Novel 1,2- bis-sulfonamide derivatives as chemokine receptor modulators

专利摘要:
The present invention relates to novel bis-sulfonamide derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of chemokine receptors.
公开号:AU2011344125A1
申请号:U2011344125
申请日:2011-12-12
公开日:2013-07-25
发明作者:Richard L. Beard；John E. Donello；Michael E. Garst；Xiaoxia Liu；Veena Viswanath；Haiqing Yuan
申请人:Allergan Inc；
IPC主号:C07D231-18

专利说明:
WO 2012/082633 PCT/US2011/064441 NOVEL 1,2- BIS-SULFONAMIDE DERIVATIVES AS CHEMOKINE RECEPTOR MODULATORS By inventors: Haiqing Yuan, Richard L. Beard, Xiaoxia Liu, John E. Donello, Veena Viswanath, and Michael E. Garst 5 RELATED APPLICATION This application claims the benefit of U.S. Provisional Application Serial No. 61/423,941, filed December 16, 2010, the disclosure of which is hereby incorporated in its entirety herein by reference. 10 FIELD OF THE INVENTION The present invention relates to novel 1,2-bis-sulfonamide derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceutical modulators of chemokine receptors. The invention 15 relates specifically to the use of these compounds and their pharmaceutical compositions to treat disorders associated with chemokine receptor (CCR) modulation. BACKGROUND OF THE INVENTION 20 Chemokines are a group of 7- to 14-kd peptides that play an important role in orchestrating leukocyte recruitment and migration during inflammation, and therefore represent an important target for anti-inflammatory therapies (Wells et al., 2006). They act by binding to seven-transmembrane, G protein-coupled receptors, the chemokine receptors. The chemokine system is complex, with about -50 25 chemokines and 20 chemokine receptors identified in humans, often acting with redundancy, making selection of specific antagonists difficult (Gerard and Rollins, 2001). Genetic knockout strategies have confirmed the importance of chemokines as regulators of immune function, but the deletion of specific chemokines has led to only specific and relatively mild defects in the inflammatory response further 30 emphasizing the complex redundancy of the system. Selectivity is crucial for use of chemokine receptor antagonists in systemic diseases where a single chemokine receptor system is implicated such as atheroscelorsis where the macrophage/monocyte system is the major player in order to allow a subtle and WO 2012/082633 PCT/US2011/064441 specific control over immune function (Weisberg et al., 2006; Feria and Diaz Gonzalez et al., 2006). Many ocular conditions are characterized by inappropriate migration and infiltration of cells such as leukocytes and endothelial cells into the eye with 5 deleterious effects to ocular structures (Wallace et al., 2004). Chemokines have been identified in such diseases and misregulation of the chemokine system is apparent in corneal graft rejection, diabetic retinopathy, age-related macular degeneration (ARMD), chronic inflammatory diseases such as uveitis, dry eye etc. Mice lacking CCR2 or MCP-1 develop features of ARMD with age, including drusen 10 deposits, choroidal neovascularization and photoreceptor atrophy indicating a crucial role for this chemokine and its receptor signaling (Amabati et al., 2003). Thus CCR2 receptor-specific inhibitor might have potential therapeutic benefit in ocular diseases like ARMD. In contrast, various human and animal studies have identified several chemokines in different forms of uveitis, produced both by resident 15 and infiltrating cells, that strongly suggests a prominent role for these molecules in its pathogenesis. Studies in rat and mice models of uveitis have demonstrated up regulation of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1), RANTES, stromal derived factor-1 (SDF-1) which are powerful chemoattractants for monocytes and T-cells (Fang et al., 2004; Keino 20 et al., 2003). Similar findings have been reported in peripheral blood mononuclear cells in patients with acute anterior uveitis (AAU), the most common form of human uveitis (Klitgaard et al., 2004). MCP-1 knockout mice and CCR5 knockout mice show reduced endotoxin-induced uveitis, which is the animal model for AAU (Takeuchi et al., 2005; Tuallion et al., 2002). It has also been demonstrated that 25 blocking the chemokine system upstream with the use of NF-KB blockers significantly attenuates experimental AAU in rats (Yang et al., 2005). Blockage of NF-KB results in transcriptional inhibition of multiple chemokines. Given the complexity of pathogenesis in uveitis it is unlikely that a selective inhibition of a chemokine receptor in monotherapy will offer therapeutic benefit. A similar role of 30 multiple chemokines have been shown to be correlated with clinical stage of disease in diabetic retinopathy and dry eye (Meleth et al., 2005; Yamagami et al., 2005). In these ocular diseases the use of broad spectrum chemokine receptor inhibitor which inhibits the function of a wide range of chemokines maybe beneficial. 2 WO 2012/082633 PCT/US2011/064441 The first broad spectrum chemokine inhibitor (BSCI) to be reported was termed Peptide 3, which was derived from the sequence of human chemokine MCP-1 and was shown to block the migration of monocytes in response to MCP-1, MIP-1, RANTES and SDF-1 (Reckless and Grainger. 1999). A cyclic retro inverse 5 analogue of Peptide 3, constructed of D-amino acids in the reverse sequence, called NR58-3.14.3 was observed to be a more potent chemokine inhibitor (Beech et al., 2001). NR58-3.14.3 has been used to test for anti-inflammatory activities in animal models of atherosclerosis, lung inflammation, irritable bowel syndrome etc (Beech et al., 2001; Grainger and Reckless. 2003; Tokuyama et al., 2005). However 10 there are several disadvantages to using these BSCI as a long-term therapeutic strategy. The known BSCIs which are peptides which have relatively low potency, poor pharmacokinetics, and are unstable in vivo. In addition, systemic use of broad spectrum chemokine receptor inhibitors could potentially lead to deleterious side effects due to their systemic anti-inflammatory activity. However in ocular diseases, 15 a local or topical application would prevent the broad spectrum inhibitor to be taken up systemically. Identification of a small molecule inhibitor of several chemokine receptors could be very useful for treatment of inflammatory ocular diseases. Given the evidence for the role of multiple chemokines in several ocular diseases and these results, we propose that the use of small and large molecule broad spectrum 20 chemokine receptor inhibitors will have utility in the local treatment of ocular inflammatory diseases including, but not limited to, uveitis, dry eye, diabetic retinopathy, allergic eye disease and proliferative retinopathies. Manipulation of multiple chemokines therefore represents a novel therapeutic approach in treating ocular diseases. 25 WO 2001028537 discloses preparation of bissulfonamide derivatives as inhibitors of dehydroquinate synthetase and type 11 dehydroquinase enzymes. Compounds N,N'-(4-chloro-1,2-phenylene)bis-2-thiophenesulfonamide (CAS 335336-21-5) and N,N'-(4-chloro-5-methyl-1,2-phenylene)bis-)2 thiophenesulfonamide (CAS 335335-03-0) are disclosed in WO 2001028537. 30 WO 2006047302 discloses bis-sulfonamide compounds as agonists of GaIR1, their preparation, pharmaceutical compositions, and use in therapy. Compounds N,N'-(1,2-phenylenebis-)-2-benzofuransulfonamide (CAS 885052-53-9) and N-[2-[[(4-chlorophenyl)sulfonyl]phenyl]- 2-benzofuransulfonamide (CAS 885052-31-3) are disclosed in WO 2006047302. 3 WO 2012/082633 PCT/US2011/064441 US7622583 discloses heteroaryl sulfonamides as antagonists of the CCR2 receptor. US 2008/0293720 discloses pyridinyl sulfonamide modulators of chemokine receptors. 5 W02005004810 discloses arylsulfonamides derivatives as bradykinin B1 antagonists or inverse agonists. W003/099773 discloses CCR9 inhibitors and methods of use thereof. W02008008374 discloses CCR2 inhibitors and methods of use thereof. 10 SUMMARY OF THE INVENTION A group of novel 1,2-bis-sulfonamide derivatives which are potent and selective chemokine receptor modulators has been discovered. As such, the compounds described herein are useful in treating a wide variety of disorders associated with modulation of chemokine receptors. The term "modulator" as used 15 herein, includes but is not limited to: receptor agonist, antagonist, inverse agonist, inverse antagonist, partial agonist, partial antagonist. This invention describes compounds of Formula I, which have chemokine receptor biological activity. The compounds in accordance with the present invention are thus of use in medicine, for example in the treatment of humans with 20 diseases and conditions that are alleviated by CCR modulation. In one aspect, the invention provides a compound having Formula I or a pharmaceutically acceptable salt thereof or stereoisomeric forms thereof, or the individual geometrical isomers, enantiomers, diastereoisomers, tautomers, zwitterions and pharmaceutically acceptable salts thereof: R6 o=s=o
R
15 N
R
3 .1R, R 1 o=s=o 25 R 5 Formula I 4 WO 2012/082633 PCT/US2011/064441 wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
2 is H or substituted or unsubstituted C1.6 alkyl;
R
3 is N or C-R ; 5 R4 is N or C-R ;
R
5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 2-benzofuran, 2 -thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 10 methylphenyl, or 4-chloro-3-trifluoromethylphenyl;
R
15 is N or C-R16;
R
17 is N or C-R18
R
7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1.s alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0
R
11 or hydroxyl; 15 R 8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1.6 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13
R
1 4 or hydroxyl;
R
16 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1.6 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 1 9 , NR 20
R
21 or hydroxyl;
R
18 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1.6 alkyl, CN, C 2-6 20 alkenyl, C 2-6 alkynyl, C(O)R 22 , NR 2 3
R
24 or hydroxyl;
R
9 is H or substituted or unsubstituted C1.6 alkyl ;
R
10 is H or substituted or unsubstituted C1.6 alkyl; R" is H or substituted or unsubstituted C1.6 alkyl;
R
12 is H or substituted or unsubstituted C1.6 alkyl 25 R 13 is H or substituted or unsubstituted C1.6 alkyl;
R
1 4 is H or substituted or unsubstituted C1.6 alkyl;
R
1 9 is H or substituted or unsubstituted C1.6 alkyl;
R
20 is H or substituted or unsubstituted C1.6 alkyl;
R
21 is H or substituted or unsubstituted C1.6 alkyl; 30 R 22 is H or substituted or unsubstituted C1.6 alkyl
R
2 3 is H or substituted or unsubstituted C1.6 alkyl;
R
24 is H or substituted or unsubstituted C1.6 alkyl; and including compounds: 5 WO 2012/082633 PCT/US2011/064441 N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}am ino)pyridin-2-yl]th iophene-2 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide; and 5 N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: a) R 6 is not the same as R5; 0 SS N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl. c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogenatoms in 10 same time atoms; d). the compound is not of the following structures: S s o o
F
3 C HN HN o CI C -- NH C S-NH o ;0 F Br OMe 0 0 o / o HN ' HN ' CI -NH -CI NH 11 / _ II / S-NH / -N CI U or 0 In another aspect, the invention provides a compound having Formula I 15 wherein: 6 WO 2012/082633 PCT/US2011/064441
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
2 is H or substituted or unsubstituted C1.6 alkyl;
R
3 is C-R ;
R
4 is C-R ; 5 R 5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 2-benzofuran, 2 -thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 methylphenyl, or 4-chloro-3-trifluoromethylphenyl; 10 R 15 is C-R 1 6 ;
R
17 is C-R 1 8
R
7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0
R
11 or hydroxyl;
R
8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 15 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13
R
1 4 or hydroxyl;
R
16 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 19 , NR 20
R
21 or hydroxyl;
R
18 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 22 , NR 2 3
R
24 or hydroxyl; 20 R 9 is H or substituted or unsubstituted C1.6 alkyl;
R
10 is H or substituted or unsubstituted C1.6 alkyl; R is H or substituted or unsubstituted C1.6 alkyl;
R
12 is H or substituted or unsubstituted C1.6 alkyl
R
13 is H or substituted or unsubstituted C1.6 alkyl; 25 R 1 4 is H or substituted or unsubstituted C1.6 alkyl;
R
1 9 is H or substituted or unsubstituted C1.6 alkyl;
R
20 is H or substituted or unsubstituted C1.6 alkyl;
R
21 is H or substituted or unsubstituted C1.6 alkyl;
R
22 is H or substituted or unsubstituted C1.6 alkyl; 30 R 2 3 is H or substituted or unsubstituted C1.6 alkyl;
R
24 is H or substituted or unsubstituted C1.6 alkyl; including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; 7 WO 2012/082633 PCT/US2011/064441 N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide; and N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: 5 a) R 6 is not the same as R5; 0 .S S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same time. d). the compound is not of the following structures: F3C HN HN O CI O CI -NH H 10 0 0 F Br OMe / CI O CI O S-NH S-NH C1 0 or 0 In another aspect, the invention provides a compound having Formula I wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl; 15 R 2 is H or substituted or unsubstituted C1.6 alkyl; 8 WO 2012/082633 PCT/US2011/064441
R
3 is N or C-R ;
R
4 is N or C-R ;
R
5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 5 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 2-benzofuran, 2 -thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 methylphenyl, or 4-chloro-3-trifluoromethylphenyl;
R
15 is N or C-R16
R
17 is N ; 10 R 7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0
R
11 or hydroxyl;
R
8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13
R
1 4 or hydroxyl;
R
16 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 15 alkenyl, C 2-6 alkynyl, C(O)R 19 , NR 20
R
21 or hydroxyl;
R
18 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 22 , NR 2 3
R
24 or hydroxyl;
R
9 is H or substituted or unsubstituted C1.6 alkyl;
R
10 is H or substituted or unsubstituted C1.6 alkyl; 20 R 1 is H or substituted or unsubstituted C1.6 alkyl;
R
12 is H or substituted or unsubstituted C1.6 alkyl
R
13 is H or substituted or unsubstituted C1.6 alkyl;
R
1 4 is H or substituted or unsubstituted C1.6 alkyl;
R
1 9 is H or substituted or unsubstituted C1.6 alkyl; 25 R 20 is H or substituted or unsubstituted C1.6 alkyl;
R
21 is H or substituted or unsubstituted C1.6 alkyl;
R
22 is H or substituted or unsubstituted C1.6 alkyl;
R
2 3 is H or substituted or unsubstituted C1.6 alkyl;
R
24 is H or substituted or unsubstituted C1-6 alkyl; 30 and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide 9 WO 2012/082633 PCT/US2011/064441 N-{4,5-d ichloro-2-[(3-th ienylsulfonyl)amino]phenyl}th iophene-2-sulfonam ide; and with the provisos: a) R 6 is not the same as R5; 0 S N b) R 5 is not C1_3 alkyl 5 c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same time; d). the compound is not of the following structures: S 0 / \ F3C HNP HNP /f 0 CI 1 CI -NH -NH 0 0 F Br OMe S o' / H N HNP CI O CI 0 -NH S-NH Cl 0 or 0 10 In another aspect, the invention provides a compound having Formula I wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
2 is H or substituted or unsubstituted C1.6 alkyl;
R
3 is C-R 15 R4 is C-R 8 10 WO 2012/082633 PCT/US2011/064441
R
5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 cycloalkenyl or is substituted or unsubstituted phenyl;
R
6 is 2-benzofuran, 2 -thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 5 methylphenyl, or 4-chloro-3-trifluoromethylphenyl;
R
15 is C-R 1 6 ;
R
17 is C-R 1 8
R
7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0
R
11 or hydroxyl; 10 R 8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13
R
1 4 or hydroxyl;
R
16 is H;
R
18 is H;
R
9 is H or substituted or unsubstituted C1.6 alkyl; 15 R1 is H or substituted or unsubstituted C1.6 alkyl;
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
12 is H or substituted or unsubstituted C1.6 alkyl
R
13 is H or substituted or unsubstituted C1.6 alkyl;
R
1 4 is H or substituted or unsubstituted C1.6 alkyl; 20 R 1 9 is H or substituted or unsubstituted C1.6 alkyl;
R
20 is H or substituted or unsubstituted C1.6 alkyl;
R
21 is H or substituted or unsubstituted C1.6 alkyl;
R
22 is H or substituted or unsubstituted C1.6 alkyl;
R
2 3 is H or substituted or unsubstituted C1.6 alkyl; 25 R 24 is H or substituted or unsubstituted C1.6 alkyl; and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 30 sulfonamide N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: a) R 6 is not the same as R5; 11 WO 2012/082633 PCT/US2011/064441 0 S I / S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same time; d). the compound is not of the following structures: 0 s s "' oS /
F
3 C HN HN'P CI S-NH -NH 5 0 0 F Br OMe s' s o1 o HN - HN ci 0Ci -NH- S-NH Ci 0 or 0 In another aspect, the invention provides a compound having Formula I wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl; 10 R 2 is H or substituted or unsubstituted C1.6 alkyl;
R
3 is C-R R 4 is C-R 8 ;
R
5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 15 cycloalkenyl or is substituted or unsubstituted phenyl;
R
6 is 2-benzofuran; 12 WO 2012/082633 PCT/US2011/064441
R
15 is C-R 1 6 ;
R
17 is C-R 1 8
R
7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0
R
11 or hydroxyl; 5 R 8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13
R
1 4 or hydroxyl;
R
16 is H;
R
18 is H;
R
9 is H or substituted or unsubstituted C1.6 alkyl; 10 R10 is H or substituted or unsubstituted C1.6 alkyl;
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
12 is H or substituted or unsubstituted C1.6 alkyl
R
13 is H or substituted or unsubstituted C1.6 alkyl;
R
1 4 is H or substituted or unsubstituted C1.6 alkyl; 15 R 1 9 is H or substituted or unsubstituted C1.6 alkyl;
R
20 is H or substituted or unsubstituted C1.6 alkyl;
R
2 1 is H or substituted or unsubstituted C1.6 alkyl;
R
22 is H or substituted or unsubstituted C1.6 alkyl;
R
2 3 is H or substituted or unsubstituted C1.6 alkyl; 20 R 24 is H or substituted or unsubstituted C1.6 alkyl; and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 25 sulfonamide N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: a) R 6 is not the same as R5; 0 S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl 13 WO 2012/082633 PCT/US2011/064441 In another aspect, the invention provides a compound having Formula I wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
2 is H or substituted or unsubstituted C1.6 alkyl; 5 R 3 is C-R ;
R
4 is C-R ;
R
5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 cycloalkenyl or is substituted or unsubstituted C610 aryl; 10 R 6 is 2 -thienyl;
R
15 is C-R 1 6 ;
R
17 is C-R 1 8
R
7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0
R
11 or hydroxyl; 15 R 8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13
R
1 4 or hydroxyl;
R
16 is H;
R
18 is H;
R
9 is H or substituted or unsubstituted C1.6 alkyl; 20 R 1 0 is H or substituted or unsubstituted C1.6 alkyl;
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
12 is H or substituted or unsubstituted C1.6 alkyl
R
13 is H or substituted or unsubstituted C1.6 alkyl;
R
1 4 is H or substituted or unsubstituted C1.6 alkyl; 25 R 1 9 is H or substituted or unsubstituted C1.6 alkyl;
R
20 is H or substituted or unsubstituted C1.6 alkyl;
R
21 is H or substituted or unsubstituted C1.6 alkyl;
R
22 is H or substituted or unsubstituted C1.6 alkyl;
R
2 3 is H or substituted or unsubstituted C1.6 alkyl; 30 R 24 is H or substituted or unsubstituted C1.6 alkyl; and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; 14 WO 2012/082633 PCT/US2011/064441 N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide N-{4,5-d ichloro-2-[(3-th ienylsulfonyl)amino]phenyl}th iophene-2-sulfonam ide; and with the provisos: 5 a) R 6 is not the same as R5; 0 -S S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same time. In another aspect, the invention provides a compound having Formula I 10 wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
2 is H or substituted or unsubstituted C1.6 alkyl;
R
3 is C-R R 4 is C-R 8 15 R5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 4-chloro-3-trifluoromethylphenyl;
R
15 is C-R 1 6 20 R 17 is C-R- 18
R
7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0
R
11 or hydroxyl;
R
8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13
R
1 4 or hydroxyl; 25 R 16 is H;
R
18 is H;
R
9 is H or substituted or unsubstituted C1.6 alkyl;
R
10 is H or substituted or unsubstituted C1.6 alkyl; R" is H or substituted or unsubstituted C1.6 alkyl; 15 WO 2012/082633 PCT/US2011/064441
R
12 is H or substituted or unsubstituted C1-6 alkyl
R
13 is H or substituted or unsubstituted C1.6 alkyl;
R
1 4 is H or substituted or unsubstituted C1.6 alkyl;
R
1 9 is H or substituted or unsubstituted C1.6 alkyl; 5 R 20 is H or substituted or unsubstituted C1.6 alkyl;
R
2 1 is H or substituted or unsubstituted C1.6 alkyl;
R
22 is H or substituted or unsubstituted C1.6 alkyl;
R
2 3 is H or substituted or unsubstituted C1.6 alkyl;
R
24 is H or substituted or unsubstituted C1.6 alkyl; 10 and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide 15 N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: a) R 6 is not the same as R5; 0 -S S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl d). the compound is not of the following structure: S0
F
3 C HN CI S-NH 20 0 In another aspect, the invention provides a compound having Formula I wherein:
R
1 is H or substituted or unsubstituted C1-6 alkyl;
R
2 is H or substituted or unsubstituted C1-6 alkyl; 16 WO 2012/082633 PCT/US2011/064441
R
3 is C-R ;
R
4 is C-R ;
R
5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 5 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl or 4-chloro-3-methylphenyl;
R
15 is C-R 1 6 ;
R
17 is C-R 1 8
R
7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 10 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0
R
11 or hydroxyl;
R
8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1.3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13
R
1 4 or hydroxyl;
R
16 is H;
R
18 is H; 15 R9 is H or substituted or unsubstituted C1.6 alkyl;
R
10 is H or substituted or unsubstituted C1.6 alkyl; R is H or substituted or unsubstituted C1.6 alkyl;
R
12 is H or substituted or unsubstituted C1.6 alkyl
R
13 is H or substituted or unsubstituted C1.6 alkyl; 20 R 1 4 is H or substituted or unsubstituted C1.6 alkyl;
R
1 9 is H or substituted or unsubstituted C1.6 alkyl;
R
20 is H or substituted or unsubstituted C1.6 alkyl;
R
21 is H or substituted or unsubstituted C1.6 alkyl;
R
22 is H or substituted or unsubstituted C1.6 alkyl; 25 R 2 3 is H or substituted or unsubstituted C1.6 alkyl;
R
24 is H or substituted or unsubstituted C1.6 alkyl; and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; 30 N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: a) R 6 is not the same as R5; 17 WO 2012/082633 PCT/US2011/064441 0 S I / S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl d). the compound is not of the following structures: Br OMe o o HNP HNP CI 0 CI N / S-NH/ o ;CI 0 or F s CI 0 /IS-NH 5 In another aspect, the invention provides a compound having Formula I wherein:
R
1 is H or substituted or unsubstituted C1-6 alkyl;
R
2 is H or substituted or unsubstituted C1-6 alkyl;
R
3 is C-R 10 R4 is C-R 8 R 5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 2-benzofuran, 2 -thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 15 methylphenyl, or 4-chloro-3-trifluoromethylphenyl; 18 WO 2012/082633 PCT/US2011/064441
R
15 is C-R 1 6 R 17 is C-R 1 8
R
7 is H, substituted or unsubstituted C1-6 alkyl;
R
8 is H, substituted or unsubstituted C1.6 alkyl; 5 R 16 is H;
R
18 is H; and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; 10 N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: a) R 6 is not the same as R5; 0 .5 N 15 b) when R 5 is a substituted heterocycle then it is not C1- 3 alkyl c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same time; d). the compound is not of the following structures: 0 S s O'
F
3 C HN HN/ 0 CI 0 CI -NH -NH 19 WO 2012/082633 PCT/US2011/064441 F Br OMe s s0 o / o HN ' HN' CIS-NH C S-NH CI 0 or 0 In another aspect, the invention provides a compound having Formula I wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl; 5 R 2 is H or substituted or unsubstituted C1.6 alkyl;
R
3 is C-R ;
R
4 is C-R 8 R 5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 10 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 2-benzofuran;
R
15 is C-R 1 6 ;
R
17 is C-R 1 8
R
7 is H, substituted or unsubstituted C1.6 alkyl; 15 R 8 is H, substituted or unsubstituted C1.6 alkyl;
R
16 is H;
R
18 is H; and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 20 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: 25 a) R 6 is not the same as R5; 20 WO 2012/082633 PCT/US2011/064441 0 S I / S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl In another aspect, the invention provides a compound having Formula I wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl; 5 R 2 is H or substituted or unsubstituted C1.6 alkyl;
R
3 is C-R ;
R
4 is C-R 8 R 5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 10 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 2 -thienyl;
R
15 is C-R 1 6 ;
R
17 is C-R 1 8
R
7 is H, substituted or unsubstituted C1.6 alkyl; 15 R 8 is H, substituted or unsubstituted C1.6 alkyl;
R
16 is H;
R
18 is H; and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 20 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: 25 a) R 6 is not the same as R5; 21 WO 2012/082633 PCT/US2011/064441 0 S I / S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same time. In another aspect, the invention provides a compound having Formula I 5 wherein:
R
1 is H or substituted or unsubstituted C1.6 alkyl;
R
2 is H or substituted or unsubstituted C1.6 alkyl;
R
3 is C-R R 4 is C-R 8 10 R 5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 cycloalkenyl or is substituted or unsubstituted C610 aryl;
R
6 is 4-chloro-3-trifluoromethylphenyl;
R
15 is C-R 1 6 15 R 17 is C-R 18 R 7 is H, substituted or unsubstituted C1.6 alkyl;
R
8 is H, substituted or unsubstituted C1.6 alkyl;
R
16 is H;
R
18 is H; 20 and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide 25 N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: a). R 6 is not the same as R5; 22 WO 2012/082633 PCT/US2011/064441 0 S I / S N a) when R 5 is a substituted heterocycle then it is not C13 alkyl d). the compound is not of the following structures:
F
3 C HN 0 CI1- S-NH -~ || In another aspect, the invention provides a compound having Formula I 5 wherein:
R
1 is H;
R
2 is H;
R
3 is C-R ;
R
4 is C-R 8 10 R 5 is 2 -thienyl, phenyl, phenyl-4-acetamide, 4-chloro-3-trifluoromethylphenyl, -1 methyl-1 H-imidazole, 3-pyridine, 2 aminophenyl, 1,3-dimethyl-1H-pyrazole, 1 methyl-1 H-pyrazole, 1-methyl-1 H-imidazole, 4-(1 H-pyrazol-1 -yl)phenyl, 1,3-thiazol 4-yl)phenyl, 4-(1,3-oxazol-5-yl)phenyl, 2-(methylamino)benzoate, 1-methyl-1 H-indole, 2 15 oxoindoline, 1-methyl-2,3-dioxoindoline, 1-methyl-2-oxoindoline, 2-furan, 4-biphenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, -3,5-dimethylisoxazole, 4-chloro-2,5 difluorophenyl, 4-(2-methylphenoxy)phenyl, 5-isoxazol-3-ylthiophene, 2,6-dichlorophenyl, 4 (methylsulfonyl)phenyl, 3,4-difluorophenyl, 4-chloro-3-methylphenyl, 2-oxo-2,3 20 dihydro-1,3-benzoxazole, 4-benzoic acid, 2-methoxybenzoic acid, 3-cyanophenyl, 4-tert-butylphenyl, 1,3-benzothiazole, 1 H-1,2,4-triazole, 2-chloro-1,3-benzothiazole, 2,4-dimethoxyphenyl, 2,5-dichloro-3-thienyl, 3-methoxyphenyl, 3 (methylsulfonyl)phenyl, 3-chloro-2-methylphenyl, 4phenylpropanoic acid, 2 23 WO 2012/082633 PCT/US2011/064441 ethoxybenzoic acid, 2-methylphenyl}acetamide, 3,5-bis(trifluoromethyl)phenyl, 1 H pyrazole, 4-(trifluoromethoxy)phenyl, 4-(benzyloxy)phenyl, 2-chloro-4-fluorobenzoic acid, thiophene-2-carboxylate, 4-fluorobenzoic acid, 2-chloro-quinoline, 2,3-dihydro 1 H-inden, 1 -nathphtyl, 1,3-benzodioxole, 3,5-dichloro-2-hydroxyphenyl, 2 5 benzofuran, quinoline, 4-methylbenzoate, 2,4-dimethyl-1,3-thiazole, 4-methyl-1,3 thiazol-2-yl}acetamide, 5-chloro-8-quinoline, 2,4,5-trifluorophenyl, 3,4 dimethoxyphenyl, 3,5-dimethyl-1H-pyrazole, 1-(phenylsulfonyl)-1H-pyrrole, N acetylindoline, 1,3,4-oxadiazol-2-yl-phenyl, 3-(1 -methyl-1 H-pyrazol-3-yl)phenyl, 2 thienylsulfonyl)amino]phenyl-4-methyl, 2-oxo-2H-chromene, 6-phenyl-3-pyridine, 2 10 chloro-4-(trifluoromethyl)phenyl, 6-phenoxypyridine, 5-phenylthiophene, 2,5 dimethyl-3-thienyl, 2-chlorophenyl-4-acetamide, (5-chloro-2,4-difluorophenyl, 4-(1 methyl-1 H-pyrazol-3-yl)phenyl, 5-methyl-1 -benzothiophene, 2,5-dimethylfuran, 4 (pyrrolidin-1-ylsulfonyl)phenyl, methyl-2-methyl-3-furoate, 3-oxo-3,4-dihydro-2H-1,4 benzoxazine, 2,4-dichloro-benzoic acid, 5-{[(dimethylamino)carbonyl]amino}-2 15 ethoxyphenyl, 2-methoxyphenyl}acetamide, 2- imidazo[2,1-b][1,3]thiazole, 6 morpholin-4-ylpyridine, 3-[(6-methylpyrazin-2-yl)oxy]phenyl, 5-pyridin-2-ylthiophene, 3-pyrimidin-2-ylphenyl, 4-dihydro-2H-pyrido[3,2-b][1,4]oxazine, 6-(dimethylamino)-2 naphthyl, 2-(methylsulfonyl)phenyl, 3-methyl-8-quinoline, 5-isoxazol-5-ylthiophene, 5-(dimethylamino)-1-naphthyl, 2-chloro-thienyl, methyl, ethyl, benzyl, isso-butyl, 2,2 20 dimethylchromane, 2-oxo-2,3,4,5-tetrahydro-1 H-1 -benzazepine, 4-methyl-3,4 dihydro-2H-1,4-benzoxazine, 4-acetyl-3,4-dihydro-2H-1,4-benzoxazine, 4 (benzyloxy)phenyl, 2,4-dimethyl-1,3-thiazole, 3,5-dimethylisoxazole, 5-chloro-3 methyl-1-benzothien-2-yl, 2-chloro-4-fluorobenzoic acid, 4-methyl-1,3-thiazol-2 yl}acetamide, 1 H-1,2,4-triazole, phenyl}propanoic acid, 5-chlorothiophene-2 25 carboxylate, 3-phenylacetamide, 2-oxoindoline, 2-oxo-2,3-dihydro-1,3-benzoxazole, 5-isoxazol-3-yl-2-thienyl, 2-chloroquinoline, 1 -(phenylsulfonyl)-i H-pyrrole, 2,5 dichloro-3-thienyl, 5-{[(dimethylamino)carbonyl]amino}-2-ethoxyphenyl, 6-morpholin 4-ylpyridine, 4-methoxythiophene, 3-furyl, 1-methyl-1 H-pyrazole, 6 chloroimidazo[2,1 -b][1,3]thiazole, 30 3-(5-methyl- 1,2,4-oxadiazol-3-yl)phenyl, 3-pyrimidin-2-ylphenyl, 1-acetyl-indoline, isonicotinate, 3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl, 4-(3,5-dimethyl-1 H-pyrazol-1 yl)phenyl, 3,5-dimethyl-1 -phenyl-1 H-pyrazole, 4-methyl-3,4-dihydro-2H-1,4 benzoxazine, 3,4-dihydro-2H-1,5-benzodioxepine, 2,2-dimethylchromane, 4-methyl 2-phenyl-1,3-thiazole, 5-pyridin-2-yl-2-thienyl, 4-methyl-3,4-dihydro-2H-pyrido[3,2 24 WO 2012/082633 PCT/US2011/064441 b][1,4]oxazine, 3-oxo-3,4-dihydro-2H-1,4-benzoxazine, 5,6-dichloro-3-pyridine, 2,3 dioxo-1,2,3,4-tetrahydroquinoxaline or 4-acetyl-3,4-dihydro-2H-1,4-benzoxazine;
R
6 is 2-benzofuran or 2 -thienyl;
R
15 is C-R 1 6 5 R 17 is N or C-R18
R
7 is H, methyl or chlorine;
R
8 is H or chlorine;
R
16 is H;
R
18 is H; and 10 with the provisos: a) R 6 is not the same as R5; b). when R 6 is 2-thienyl then R , R , R 16 and R 18 are not all hydrogen in same time. The term "alkyl", as used herein, refers to saturated, monovalent or divalent 15 hydrocarbon moieties having linear or branched moieties or combinations thereof and containing 1 to 6 carbon atoms. One methylene (-CH 2 -) group, of the alkyl can be replaced by oxygen, sulfur, sulfoxide, nitrogen, carbonyl, carboxyl, sulfonyl, or by a divalent C 3-6 cycloalkyl. Hydrogen atoms on alkyl groups can be substituted by groups including, but not limited to: halogens, -OH, C 3.8 cycloalkyl, non-aromatic 20 heterocycles, aromatic heterocycles, -OC1.6 alkyl, -NH 2 , -NO 2 , amides, ethers, esters, aldehydes, ketones, sulfonamides groups, aryl, carboxylic acid and derivatives such as esters and amides, phosphonic acid groups, sulphonic acid groups, phosphoric acid. The term "cycloalkyl", as used herein, refers to a monovalent or divalent 25 group of 3 to 12 carbon atoms, derived from a saturated cyclic hydrocarbon. Cycloalkyl groups can be monocyclic or polycyclic. Cycloalkyl can be substituted by groups including, but not limited to: halogens, -OH, C 3.8 cycloalkyl, non-aromatic heterocycles, aromatic heterocycles, -OC1.6 alkyl, -NH 2 , -NO 2 , amides, ethers, esters, aldehydes, sulfonamides groups, aryl, carboxylic acid and derivatives such 30 as esters and amides, phosphonic acid groups, sulphonic acid groups, phosphoric acid. The term "cycloalkenyl", as used herein, refers to a monovalent or divalent group of 3 to 12 carbon atoms, derived from a saturated cycloalkyl having one or more double bond. Cycloalkenyl groups can be monocyclic or polycyclic. 25 WO 2012/082633 PCT/US2011/064441 Cycloalkenyl groups can be substituted by groups including, but not limited to: halogens, -OH, C 3-8 cycloalkyl, non-aromatic heterocycles, aromatic heterocycles, -OC1.6 alkyl, -NH 2 , -NO 2 , amides, ethers, esters, aldehydes, sulfonamides groups, aryl, carboxylic acid and derivatives such as esters and amides, phosphonic acid 5 groups, sulphonic acid groups, phosphoric acid. The term "halogen", as used herein, refers to an atom of chlorine, bromine, fluorine, iodine. The term "alkenyl", as used herein, refers to a monovalent or divalent hydrocarbon radical having 2 to 6 carbon atoms, derived from a saturated alkyl, having at least one double bond. C 2-6 alkenyl can be in the E or Z configuration. 10 Alkenyl groups can be substituted by groups including, but not limited to: halogens, -OH, C 3.8 cycloalkyl, non-aromatic heterocycles, aromatic heterocycles, -OC1.6 alkyl, -NH 2 , -NO 2 , amides, ethers, esters, aldehydes, sulfonamides groups, aryl, carboxylic acid and derivatives such as esters and amides, phosphonic acid groups, sulphonic acid groups, phosphoric acid The term "alkynyl", as used herein, refers 15 to a monovalent or divalent hydrocarbon radical having 2 to 6 carbon atoms, derived from a saturated alkyl, having at least one triple bond. The term "heterocycle" as used herein, refers to a 3 to 12 membered ring, which can be aromatic or non-aromatic, saturated or non-saturated, containing at least one heteroatom selected from 0 or N or S or combinations of at least two 20 thereof, interrupting the carbocyclic ring structure. The heterocyclic ring can be interrupted by a C=0; the S heteroatom can be oxidized. Heterocycles can be monocyclic or polycyclic. Heterocyclic ring moieties can be substituted by groups including, but not limited to: halogens, -OH, C 3.8 cycloalkyl, non-aromatic heterocycles, aromatic heterocycles, -OC1.6 alkyl, -NH 2 , -NO 2 , amides, ethers, 25 esters, aldehydes, ketones, sulfonamides groups, aryl, carboxylic acid and derivatives such as esters and amides, phosphonic acid groups, sulphonic acid groups, phosphoric acid. Usually, in the present case, heterocyclic groups are pyridine, furan, azetidine, thiazol, thiophene, oxazol, pyrazol, benzofuran, isoxazole, 2-oxoindoline, 30 2-oxo-2,3-dihydro-1,3-benzoxazole, 2-oxo-2H-chromene, imidazole[2,1-b]thiazolel H-pyrazole, indole, imidazole, quinoline. The term "aryl" as used herein, refers to an organic moiety derived from an aromatic hydrocarbon consisting of a ring containing 6 to 10 carbon atoms. By removal of one hydrogen, aryl can be substituted by groups including, but not 26 WO 2012/082633 PCT/US2011/064441 limited to: halogens, -OH, C 3-8 cycloalkyl, non-aromatic heterocycles, aromatic heterocycles, -OC1.6 alkyl, -NH 2 , -NO 2 , amides, ethers, esters, aldehydes, ketones, sulfonamides groups, aryl, carboxylic acid and derivatives such as esters and amides, phosphonic acid groups, sulphonic acid groups, phosphoric acid. Aryl can 5 be monocyclic or bicyclic. The term "ketone" as used herein, represents a group of formula "-C(O) RX" wherein RX is C 1-6 alkyl. The term "hydroxyl" as used herein, represents a group of formula "-OH". The term "amino" as used herein, represents a group of formula "-NH 2 ". 10 The term "carbonyl" as used herein, represents a group of formula "-C(O)". The term "carboxyl" as used herein, represents a group of formula "-C(0)0-". The term "sulfonyl" as used herein, represents a group of formula "-SO 2 -". The term "sulfate" as used herein, represents a group of formula "-O-S(0) 2 -0 15 The term "carboxylic acid" as used herein, represents a group of formula C(O)OH". The term "sulfoxide" as used herein, represents a group of formula "-S=O". The term "phosphonic acid" as used herein, represents a group of formula
P(O)(OH)
2 ". 20 The term "phosphoric acid" as used herein, represents a group of formula
(O)P(O)(OH)
2 ". The term "sulphonic acid" as used herein, represents a group of formula
S(O)
2 0H". The formula "H ", as used herein, represents a hydrogen atom. 25 The formula "0 ", as used herein, represents an oxygen atom. The formula "N ", as used herein, represents a nitrogen atom. The formula "S ", as used herein, represents a sulfur atom. The term "amine" as used herein, represents a group of formula "-NRxRy ",wherein RX and RY can be the same or independently H, alkyl, aryl, cycloalkyl, 30 cycloalkenyl, heterocycle as defined above. The term "amide" as used herein, represents a group of formula C(O)NRxR," or "-C(O)N(R)(R)" or "NRxC(O)R" wherein RX and RY can be the same or independently H, alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycle as defined above. 27 WO 2012/082633 PCT/US2011/064441 The term "sulfonamide" as used herein, represents a group of formula "
S(O)
2 NRxR" or "NRxRYS(O) 2 " or "-NRxS(O) 2 RY wherein RX and RY can be the same or independently H, alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycle as defined above. 5 The term "ester" as used herein, represents a group of formula "-C(O)O(RX)", wherein RX is alkyl, aryl, cycloalkyl, cycloalkenyl, heterocycle as defined above. The term "aldehyde" as used herein, represents a group of formula "-C(O)H". Some compounds of the invention are: N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 10 sulfonamide; N-{4,5-dichloro-2-[(phenylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}acetamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 15 methylphenyl]thiophene-2-sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -methyl-1 H imidazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 methylphenyl]pyridine-3-sulfonamide; 20 N-(2-{[(4-aminophenyl)sulfonyl]amino}-5-chlorophenyl)-4-chloro-3 (trifluoromethyl)benzenesulfonamide; 5-chloro-N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 methylphenyl]-1,3-dimethyl-1 H-pyrazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 25 1,3,5-trimethyl-1 H-pyrazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 1-methyl-1 H-pyrazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 1-methyl-1 H-imidazole-4-sulfonamide; 30 4-chloro-N-{4-chloro-5-methyl-2-[(phenylsulfonyl)amino]phenyl}-3 (trifluoromethyl)benzenesulfonamide; 4-chloro-N-{5-chloro-2-[(phenylsulfonyl)amino]phenyl}-3 (trifluoromethyl)benzenesulfonamide; 28 WO 2012/082633 PCT/US2011/064441 N-[4,5-dichloro-2-({[4-(l H-pyrazol-1-yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[4-(l H-pyrazol-1-yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; 5 N-[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene 2-sulfonamide; N-[4,5-dichloro-2-({[4-(2-methyl-1,3-thiazol-4 yl)phenyl]sulfonyl}amino)phenyl]th iophene-2-sulfonam ide; N-[4,5-dichloro-2-({[4-(2-methyl-1,3-thiazol-4 10 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[4-(1,3-oxazol-5-yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 (methylam ino)benzoate; 15 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 (methylamino)benzoic acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-indole-5 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxoindoline-5-sulfonamide; 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxoindoline-5-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-2,3-dioxoindoline-5 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-2-oxoindoline-5 sulfonamide; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-2-sulfonamide; N-{2-[(biphenyl-4-ylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide; N-(4,5-dichloro-2-{[(3,5-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3,5-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 30 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-3,5-di methyl isoxazole-4 sulfonamide; N-(4,5-dichloro-2-{[(4-chloro-2,5-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 29 WO 2012/082633 PCT/US2011/064441 N-[4,5-dichloro-2-({[4-(2-methylphenoxy)phenyl]sulfonyl}amino)phenyl]th iophene-2 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-5-isoxazol-3-ylth iophene-2 sulfonamide; 5 N-(4,5-dichloro-2-{[(2,4-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2,6-dichlorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-fluorophenyl)sulfonyl]am ino}phenyl)th iophene-2-sulfonam ide; 10 N-[4,5-dichloro-2-({[4-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3,4-difluorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; 15 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-methyl-1 benzothiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(4-chloro-3-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3-dihydro-1,3 20 benzoxazole-6-sulfonamide; 4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methoxybenzoic acid; N-(4,5-d ichloro-2-{[(3-chloro-4-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 25 sulfonamide; N-(4,5-dichloro-2-{[(3-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(4-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; N-(2-{[(4-tert-butylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2 sulfonamide; 30 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzothiazole-6 sulfonamide; N-(4,5-dichloro-2-{[(2-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 H-1,2,4-triazole-5-sulfonamide; 30 WO 2012/082633 PCT/US2011/064441 2-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzothiazole-6 sulfonamide; N-(4,5-d ichloro-2-{[(3,4-dimethylphenyl)sulfonyl]am ino}phenyl)th iophene-2 sulfonamide; 5 N-(4,5-dichloro-2-{[(2,4-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2,5-dichloro-3-th ienyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-methoxyphenyl)sulfonyl]am ino}phenyl)th iophene-2 10 sulfonamide; N-[4,5-dichloro-2-({[4-(trifl uoromethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; 15 N-[4,5-dichloro-2-({[3-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; 3-{4-[({4,5-dichloro-2-[(2 20 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}propanoic acid; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-ethoxybenzoic acid; N-{4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methylphenyl}acetamide; 25 N-[2-({[3,5-bis(trifluoromethyl)phenyl]sulfonyl}amino)-4,5-dichlorophenyl]thiophene 2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 H-pyrazole-4-sulfonamide; N-(4,5-dichloro-2-{[(3-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[4-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 30 sulfonamide; N-[2-({[4-(benzyloxy)phenyl]sulfonyl}amino)-4,5-dichlorophenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 31 WO 2012/082633 PCT/US2011/064441 2-chloro-5-[({4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 fluorobenzoic acid; methyl 5-chloro-3-[({4,5-dichloro-2-[(2 thienylsulfonyl)am ino] phenyl}am ino)sulfonyl]th iophene-2-carboxylate; 5 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4-fluorobenzoic acid; 2-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-6-sulfonamide; N-(4,5-dichloro-2-{[(5-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 10 N-{4,5-dichloro-2-[(2,3-dihydro-1 H-inden-5-ylsulfonyl)amino]phenyl}thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(4-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(1 -naphthylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzodioxole-5-sulfonamide; 15 N-[4,5-dichloro-2-({[2-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]amino}phenyl)thiophene 2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-5-sulfonamide; 20 N-(4,5-dichloro-2-{[(2,6-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-3-sulfonamide; N-(4,5-dichloro-2-{[(2,3-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 methyl 4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-8-sulfonamide; N-(4,5-dichloro-2-{[(2-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-2,4-dimethyl-1,3-thiazole-5 sulfonamide; 30 N-(4,5-dichloro-2-{[(3-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4-methyl-1 ,3 thiazol-2-yl}acetamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}isoquinoline-5-sulfonamide; 32 WO 2012/082633 PCT/US2011/064441 5-chloro-N-{4,5-d ichloro-2-[(2-thienylsulfonyl)am ino]phenyl}qu inol ine-8-sulfonam ide; N-(4,5-d ichloro-2-{[(2,5-dichlorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2,4,5-trifluorophenyl)sulfonyl]am ino}phenyl)th iophene-2 5 sulfonamide; N-(4,5-d ichloro-2-{[(3,4-d imethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2-methoxyphenyl)sulfonyl]am ino}phenyl)th iophene-2 sulfonamide; 10 N-[4,5-dichloro-2-({[3-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; methyl 3-[({4,5-dichloro-2-[(2 thienylsulfonyl)am ino] phenyl}am ino)sulfonyl]th iophene-2-carboxylate; N-(4,5-dichloro-2-{[(2,5-difluorophenyl)sulfonyl]amino}pheny)thiophene-2 15 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,5-dimethyl-1 H-pyrazole-4 sulfonamide; N-(4,5-dichloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-6-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -(phenylsulfonyl)-l H-pyrrole-3 sulfonamide; N-(4,5-dichloro-2-{[(3,5-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 N-(4,5-dichloro-2-{[(4-methoxy-3-methylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-pyrazole-5 30 sulfonamide; 1 -acetyl-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}indoline-5-sulfonamide; N-[4,5-dichloro-2-({[3-(5-methyl-1,3,4-oxadiazol-2 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 33 WO 2012/082633 PCT/US2011/064441 N-[4,5-dichloro-2-({[3-(l -methyl-1 H-pyrazol-3 yl)phenyl]sulfonyl}amino)phenyl]th iophene-2-sulfonam ide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-4-methyl-2-phenyl-1,3-thiazole 5-sulfonamide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-methylbenzoic acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-1,2,3,4 tetrahydroquinoline-6-sulfonamide; 10 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2H-chromene-6 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-phenylpyridine-3-sulfonamide; ethyl 3-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]isonicotinate; 15 N-[4,5-dichloro-2-({[2-chloro-4 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-1 -benzofuran-5 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-phenoxypyridine-3 20 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-phenylthiophene-2 sulfonamide; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4-methylbenzoic acid; 25 N-(4,5-dichloro-2-{[(2,5-dimethyl-3-thienyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{2-chloro-4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}acetamide; N-(4,5-dichloro-2-{[(5-chloro-2,4-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 30 sulfonamide; N-[4,5-dichloro-2-({[4-(1 -methyl-1 H-pyrazol-3 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methyl-1 -benzothiophene-2 sulfonamide; 34 WO 2012/082633 PCT/US2011/064441 N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)am ino]phenyl}-2,5-d imethylfuran-3-sulfonam ide; N-[4,5-dichloro-2-({[4-(pyrrolidin-1 ylsulfonyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-methyl 5 3-furoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-oxo-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; 2,4-dichloro-5-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 10 N-[4,5-dichloro-2-({[4-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(5-{[(d imethylam ino)carbonyl]amino}-2 ethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 15 methoxyphenyl}acetamide; 6-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}imidazo[2,1 b][1,3]thiazole-5-sulfonamide; N-[4,5-dichloro-2-({[3-(1 -methyl-1 H-pyrazol-5 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 20 methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-1 -methyl 1 H-pyrrole-2-carboxylate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methylfuran-2-sulfonamide; N-[4,5-dichloro-2-({[4-(phenoxymethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide; 25 N-(4,5-dichloro-2-{[(4-phenoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 5,6-dichloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3 sulfonamide; N-(4,5-d ichloro-2-{[(2-fluoro-4-methyl phenyl)sulfonyl]am ino}phenyl)th iophene-2 30 sulfonamide; N-(4,5-dichloro-2-{[(2-ethoxy-5 {[(methylamino)carbonyl]am ino}phenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 35 WO 2012/082633 PCT/US2011/064441 N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-6-morphol in-4-ylpyrid ine-3 sulfonamide; N-{4,5-d ichloro-2-[({3-[(6-methylpyrazin-2 yl)oxy]phenyl}sulfonyl)am ino]phenyl}thiophene-2-sulfonamide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}chromane-6-sulfonamide; N-[4,5-dichloro-2-({[4-(3,5-dimethyl-1 H-pyrazol-1 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methylthiophene-2 sulfonamide; 10 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 hydroxybenzoic acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2,4-dichloro-5-methyl phenyl)sulfonyl]amino}phenyl)th iophene-2 15 sulfonamide; N-[4,5-dichloro-2-({[4-fluoro-3 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoate; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 20 methoxyth iophene-3-carboxylate; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 furoate; N-(4,5-dichloro-2-{[(2-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-1 H-pyrazole-3 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-1 H-indole-7 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-pyridin-2-ylthiophene-2 30 sulfonamide; N-(4,5-dichloro-2-{[(4'-fluorobiphenyl-4-yl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-fluoro-4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 36 WO 2012/082633 PCT/US2011/064441 N-(4,5-d ichloro-2-{[(3-chloro-2-fluorophenyl)sulfonyl]am ino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3-dihydro-1,3 benzothiazole-6-sulfonam ide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-3-sulfonamide; N-[4,5-dichloro-2-({[3-(5-methyl-1,2,4-oxadiazol-3 yl)phenyl]sulfonyl}amino)phenyl]th iophene-2-sulfonam ide; ethyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-3-furoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,4-dihydro-2H-1,5 10 benzodioxepine-7-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-1 -benzofuran-7 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-methyl-1,3-benzothiazole-6 sulfonamide; 15 N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-1,3,5-trimethyl-1 H-pyrazole-4 sulfonamide; N-(4,5-dichloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-cyano-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 20 sulfonamide; N-{5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-1,3-thiazol-2 yl}acetam ide; N-{4,5-d ichloro-2-[({4-[(6-methylpyrazin-2 yl)oxy]phenyl}sulfonyl)amino]phenyl}thiophene-2-sulfonamide; 25 N-(4,5-dichloro-2-{[(3-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxybenzoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-3 30 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-4-methyl-3,4-dihydro-2H pyrido[3,2-b][1,4]oxazine-7-sulfonamide; 5-chloro-N-{4,5-dichloro-2-[(2-thienysulfonyl)amino]phenyl}-1,3-dimethyl-1 H pyrazole-4-sulfonamide; 37 WO 2012/082633 PCT/US2011/064441 N [(1,5 dichloro 2 [(3 th ienYlcu foRYl)aMiOE] phenyl) th OEphene 2 culfonamide; N-(4,5-dichloro-2-{[(5-chloro-2-naphthyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{2-[(biphenyl-3-ylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide; 5 N-(4,5-dichloro-2-{[(2-fluoro-5-methylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 4-chloro-3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 10 methoxybenzoic acid; N-[4,5-dichloro-2-({[4-(pyridin-2-yloxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-naphthylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 15 N-[4,5-dichloro-2-({[6-(dimethylamino)-2-naphthyl]sulfonyl}amino)phenyl]thiophene 2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; N-(4,5-dichloro-2-{[(4'-chlorobiphenyl-4-yl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 20 N-(2-{[(3-acetylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dioxo-1,2,3,4 tetrahydroquinoxaline-6-sulfonamide; N-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzyl}acetamide; 25 N-[4,5-dichloro-2-({[3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[2-(methylsulfonyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-methylquinoline-8 30 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-1,4-benzodioxine-6 sulfonamide; N-[4,5-dichloro-2-({[3-(2-methylpyrimidin-4 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 38 WO 2012/082633 PCT/US2011/064441 6-chloro-N-{4,5-d ichloro-2-[(2-thienylsulfonyl)am ino]phenyl}pyrid ine-3-sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-6-methoxypyrid ine-3 sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 5 methylbenzoate; N-(4,5-dichloro-2-{[(2,5-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(2-{[(4-acetylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2-sulfonamide; methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 10 methylbenzoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-isoxazol-5-ylthiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-(1,3-oxazol-5-yl)thiophene-2 sulfonamide; 15 N-(4,5-dichloro-2-{[(5-chloro-2-methylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[5-(dimethylamino)-1 -naphthyl]sulfonyl}amino)phenyl]thiophene 2-sulfonamide; methyl 2-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 20 methoxybenzoate; 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(4-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 N-{4,5-dichloro-2-[(methylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-(4,5-dichloro-2-{[(3,5-dichloro-4-hydroxyphenyl)sulfonyl]amino}phenyl)thiophene 2-sulfonamide; N-[4,5-dichloro-2-({[4-chloro-3 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 30 2-chloro-5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; N-[4,5-dichloro-2-({[4-(pyridin-3-yloxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; 39 WO 2012/082633 PCT/US2011/064441 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-imidazole-4 sulfonamide; N-{4,5-d ichloro-2-[(ethylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-(4,5-dichloro-2-{[(4-chloro-2-fluoro-5 5 methylphenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-fluorobenzoic acid; N-{2-[(biphenyl-2-ylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide; N-{3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 10 methylphenyl}acetamide; N-(2-{[(5-tert-butyl-2-methylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2 sulfonamide; N-{2-[(benzylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide N-{4,5-dichloro-2-[(isobutylsulfonyl)amino]phenyl}thiophene-2-sulfonamide 15 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,2-dimethylchromane-6 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,2-dimethyl-1 H-imidazole-4 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3,4,5-tetrahydro-1 H-1 20 benzazepine-7-sulfonamide; N-(4,5-dichloro-2-{[(4-cyclohexylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 4-chloro-N-1 -- {4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}benzene-1,3 disulfonamide; 25 N-(4,5-dichloro-2-{[(4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{3-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}acetamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-indole-4 sulfonamide; 30 N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 40 WO 2012/082633 PCT/US2011/064441 N-{4,5-d ichloro-2-[(5,6,7,8-tetrahydronaphthalen-2 ylsulfonyl)amino]phenyl}th iophene-2-sulfonam ide; N-[4,5-dichloro-2-({[4-(2-chlorophenoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; 5 N-(4,5-dichloro-2-{[(4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; 2-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}am ino)sulfonyl]phenoxy}acetam ide; 10 N-(4,5-dichloro-2-{[(2,4-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,5-dimethyl-1 -phenyl-1 H pyrazole-4-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-4-methyl-3,4-dihydro-2H-1,4 15 benzoxazine-6-sulfonamide; 2-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; 4-acetyl-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; N-(4,5-dichloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 20 sulfonamide; N-{5-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{4-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{5-chloro-2-[(methylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-imidazole-4 25 sulfonamide; N-{2-[(benzylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; 30 N-(5-chloro-2-{[(4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; 41 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(4-chlorophenyl)sulfonyl]am ino}phenyl)-1 -benzofuran-2-sulfonamide; N-{5-chloro-2-[(2-naphthylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-8-sulfonamide; N-(5-chloro-2-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 5 sulfonamide; N-(5-chloro-2-{[(2,4-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(biphenyl-4-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-[5-chloro-2-({[4-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 10 sulfonamide; N-(5-chloro-2-{[(4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 15 N-[5-chloro-2-({[4-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-{5-chloro-2-[(1 -naphthylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2-chlorophenyl)sulfonyl]am ino}phenyl)-1 -benzofuran-2-sulfonamide; N-[5-chloro-2-({[3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 20 sulfonamide; N-(5-chloro-2-{[(2-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 25 N-(5-chloro-2-{[(3,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(2-{[(4-tert-butylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 30 sulfonamide; N-[2-({[4-(benzyloxy)phenyl]sulfonyl}amino)-5-chlorophenyl]-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3-benzodioxole-5 sulfonamide; 42 WO 2012/082633 PCT/US2011/064441 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,4-dimethyl-1,3-thiazole-5 sulfonamide; N-[5-chloro-2-({[3-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 5 N-(5-chloro-2-{[(3,5-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{5-chloro-2-[(2-furylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 10 N-{2-[(1 -benzothien-3-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3-benzothiazole-6 sulfonamide; N-[5-chloro-2-({[3-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 15 sulfonamide; N-(5-chloro-2-{[(2-fluorophenyl)sulfonyl]am ino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2,5-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[2-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 20 sulfonamide; N-(5-chloro-2-{[(5-chloro-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 25 methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]th iophene-2-carboxylate; N-{5-chloro-2-[(ethylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethylisoxazole-4 sulfonamide; 30 N-(5-chloro-2-{[(5-chloro-3-methyl-1 -benzothien-2-yl)sulfonyl]amino}phenyl)-1 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 43 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{5-chloro-2-[(isobutylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2-chloro-4 5 fluorobenzoic acid; N-{5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methyl-1,3-thiazol-2-yl}acetamide; N-(5-chloro-2-{[(2,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 10 N-(5-chloro-2-{[(4-chloro-2,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4-chloro-3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 H-1,2,4-triazole-5 15 sulfonamide; 3-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]phenyl}propanoic acid; methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-5 chlorothiophene-2-carboxylate; 20 N-{2-[(1 -benzofuran-5-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 sulfonamide; N-{3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]phenyl}acetamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxoindoline-5 25 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethyl-1 H-pyrazole 4-sulfonamide; N-[5-chloro-2-({[4-(2-methylphenoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 30 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3-dihydro-1,3 benzoxazole-6-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloro-1,3-benzothiazole 6-sulfonamide; 44 WO 2012/082633 PCT/US2011/064441 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 ethoxybenzoic acid; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 fluorobenzoic acid; 5 N-(5-chloro-2-{[(2,6-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}isoquinoline-5-sulfonamide; N-(5-chloro-2-{[(2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 10 N-(5-chloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(5-isoxazol-3-yl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]benzoic 15 acid; N-(5-chloro-2-{[(3,4-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]benzoic acid; 20 N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylphenyl}acetamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloroquinoline-6 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-3-sulfonamide; 25 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5-chloroquinoline-8 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-6-sulfonamide; N-(5-chloro-2-{[(2,4-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 30 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methoxybenzoic acid; N-(5-chloro-2-{[(2,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 45 WO 2012/082633 PCT/US2011/064441 N-[2-({[3,5-bis(trifluoromethyl)phenyl]sulfonyl}amino)-5-chlorophenyl]-1 -benzofuran 2-sulfonamide; N-(5-chloro-2-{[(5-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide 5 N-(5-chloro-2-{[(2,3-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,5-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -(phenylsulfonyl)-1 H pyrrole-3-sulfonamide; N-(5-chloro-2-{[(2,6-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 15 N-(5-chloro-2-{[(3-chloro-4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[2-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,5-dichloro-3-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 H-pyrazole-4 sulfonamide; N-{5-chloro-2-[(2,3-dihydro-1 H-inden-5-ylsulfonyl)amino]phenyl}-1 -benzofuran-2 sulfonamide; 25 methyl 4-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]benzoate; N-(5-chloro-2-{[(2,4,5-trifluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 30 sulfonamide; N-(5-chloro-2-{[(4-methoxy-3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-1,2,3,4 tetrahydroquinoline-6-sulfonamide; 46 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(5-{[(d imethylam ino)carbonyl]am ino}-2 ethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2-ethoxy-5 {[(methylamino)carbonyl]amino}phenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 5 sulfonamide; N-(2-{[(4-acetylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2-sulfonamide; methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]benzoate; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3-dihydro-1,3 10 benzothiazole-6-sulfonamide; N-{5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-1,3 thiazol-2-yl}acetamide; N-(5-chloro-2-{[(3-chloro-4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 15 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2H-chromene-6 sulfonamide; N-(5-chloro-2-{[(5-chloro-2,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 20 methoxyphenyl}acetamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-morpholin-4-ylpyridine-3 sulfonamide; methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxyth iophene-3-carboxylate; 25 N-{5-chloro-2-[(3-furylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{5-chloro-2-[({4-[(6-methylpyrazin-2-yl)oxy]phenyl}sulfonyl)amino]phenyl}-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-pyrazole-5 sulfonamide; 30 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-phenylpyridine-3 sulfonamide; N-[5-chloro-2-({[4-(1 -methyl-1 H-pyrazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 47 WO 2012/082633 PCT/US2011/064441 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-chloroimidazo[2, 1 b][1,3]thiazole-5-sulfonamide; N-{5-chloro-2-[({3-[(6-methylpyrazin-2-yl)oxy]phenyl}sulfonyl)amino]phenyl}-1 benzofuran-2-sulfonamide; 5 methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 furoate; N-[5-chloro-2-({[3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; 1 -acetyl-N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}indoline-5 sulfonamide; ethyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl] ison icotinate; 15 N-(5-chloro-2-{[(5-methyl-1 -benzothien-2-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[3-(1 -methyl-1 H-pyrazol-5-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}chromane-6-sulfonamide; 20 N-(5-chloro-2-{[(2-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; ethyl 5-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-3 furoate; methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 25 methoxybenzoate; N-(5-chloro-2-{[(4-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)-1-benzofuran-2 sulfonamide; N-[5-chloro-2-({[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 30 N-[5-chloro-2-({[2-chloro-4-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2,5-dimethyl-3-furyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 48 WO 2012/082633 PCT/US2011/064441 methyl 5-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-1 methyl-1 H-pyrrole-2-carboxylate; N-[5-chloro-2-({[4-(3,5-dimethyl-1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 5 N-(5-chloro-2-{[(4-chloro-2-fluoro-5-methylphenyl)sulfonyl]amino}phenyl)-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-pyrazole-3 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethyl-1 -phenyl-1 H 10 pyrazole-4-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-3,4-dihydro-2H 1,4-benzoxazine-6-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,4-dihydro-2H-1,5 benzodioxepine-7-sulfonamide; 15 N-[5-chloro-2-({[3-(1 -methyl-1 H-pyrazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{5-chloro-2-[(2,3-dihydro-1 -benzofuran-5-ylsulfonyl)amino]phenyl}-1 -benzofuran 2-sulfonamide; N-[5-chloro-2-({[4-(pyrrolidin-1 -ylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 20 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(5-methyl-2-furyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(5-methyl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 25 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-indole-7 sulfonamide; N-{5-chloro-2-[(2,3-dihydro-1 -benzofuran-7-ylsulfonyl)amino]phenyl}-1 -benzofuran 2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,2-dimethylchromane-6 30 sulfonamide; N-[5-chloro-2-({[4-(2-methyl-1,3-thiazol-4-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-2-phenyl-1 ,3 thiazole-5-sulfonamide; 49 WO 2012/082633 PCT/US2011/064441 N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-phenoxypyridine-3 sulfonamide; methyl 5-[({2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methyl-3-furoate; 5 N-[5-chloro-2-({[4-(phenoxymethyl)phenyl]sulfonyl}amino)phenyl]-l -benzofuran-2 sulfonamide; 5-[({2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 hydroxybenzoic acid; N-(5-chloro-2-{[(5-pyridin-2-yl-2-thienyl)sulfonyl]amino}phenyl)-l -benzofuran-2 10 sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-methyl-1,3 benzothiazole-6-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-3,4-dihydro-2H pyrido[3,2-b][1,4]oxazine-7-sulfonamide; 15 N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-indole-4 sulfonamide; N-(5-chloro-2-{[(5-phenyl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 20 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3-oxo-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; N-(5-chloro-2-{[(4-phenoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzothien-2-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 25 sulfonamide; N-(5-chloro-2-{[(4'-fluorobiphenyl-4-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3,5-trimethyl-1 H pyrazole-4-sulfonamide; 30 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5-chloro-1,3-dimethyl-1 H pyrazole-4-sulfonamide; 2-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]phenoxy}acetamide; 50 WO 2012/082633 PCT/US2011/064441 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylbenzoic acid; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methylbenzoic acid; 5 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2,4 dichlorobenzoic acid; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5,6-dichloropyridine-3 sulfonamide; N-(5-chloro-2-{[(2,4-dichloro-5-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran 10 2-sulfonamide; N-(5-chloro-2-{[(3-fluoro-4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 15 N-[5-chloro-2-({[4-(1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,5-dimethyl-3-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 20 sulfonamide; N-(5-chloro-2-{[(2-fluoro-4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-fluoro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 25 N-(5-chloro-2-{[(3-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-cyano-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(5-chloro-2-naphthyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 30 sulfonamide; N-{2-[(biphenyl-3-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloropyridine-3 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}pyridine-3-sulfonamide; 51 WO 2012/082633 PCT/US2011/064441 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,3-dihydro-1,4 benzodioxine-6-sulfonamide; N-(5-chloro-2-{[(5-isoxazol-5-yl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5 N-(5-chloro-2-{[(3,5-dichloro-4-hydroxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran 2-sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 fluorobenzoic acid; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,2-dimethyl-1 H-imidazole 10 4-sulfonamide; N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2-fluoro-5-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 15 N-(5-chloro-2-{[(4'-chlorobiphenyl-4-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[3-(2-methylpyrimidin-4-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-[5-chloro-2-({[5-(1,3-oxazol-5-yl)-2-thienyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 20 sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{2-[(biphenyl-2-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3,4,5-tetrahydro 25 1 H-1 -benzazepine-7-sulfonamide; N-(5-chloro-2-{[(3-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 chlorobenzoic acid; 30 N-(2-{[(3-acetylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-chloropyridine-3 sulfonamide; N-(5-chloro-2-{[(5-chloro-2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 52 WO 2012/082633 PCT/US2011/064441 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 chlorobenzoic acid; N-{3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methylphenyl}acetamide; 5 N-(5-chloro-2-{[(4-cyclohexylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{5-chloro-2-[(5,6,7,8-tetrahydronaphthalen-2-ylsulfonyl)amino]phenyl}-1 benzofuran-2-sulfonamide; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 10 methoxybenzoic acid; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,3-dioxo-1,2,3,4 tetrahydroquinoxaline-6-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-methoxypyridine-3 sulfonamide; 15 4-acetyl-N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,4-dihydro-2H 1,4-benzoxazine-6-sulfonamide; N-[5-chloro-2-({[5-(dimethylamino)-1 -naphthyl]sulfonyl}amino)phenyl]-1 -benzofuran 2-sulfonamide; N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 20 chlorophenyl}acetamide; N-[5-chloro-2-({[4-(pyridin-3-yloxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(2-{[(5-tert-butyl-2-methylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 sulfonamide; 25 N-1 -- {2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-chlorobenzene-1,3 disulfonamide; N-[5-chloro-2-({[4-(2-chlorophenoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(pyridin-2-yloxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 30 sulfonamide; N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]benzyl}acetamide; methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylbenzoate; 53 WO 2012/082633 PCT/US2011/064441 methyl 2-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxybenzoate; methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylbenzoate; 5 N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3-methylquinoline-8 sulfonamide; N-[5-chloro-2-({[6-(dimethylamino)-2-naphthyl]sulfonyl}amino)phenyl]-1 -benzofuran 2-sulfonamide; N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 10 sulfonamide; N-[5-chloro-3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2 yl]thiophene-2-sulfonamide. Preferred compounds of the invention are: 15 N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-pyrazole-3 sulfonamide; N-(5-chloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; 20 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-chloroimidazo[2, 1 b][1,3]thiazole-5-sulfonamide; N-(4,5-d ichloro-2-{[(2-fluoro-5-methyl phenyl)sulfonyl]am ino}phenyl)th iophene-2 sulfonamide; N-(5-chloro-2-{[(2,6-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 25 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5-chloro-1,3-dimethyl-1 H pyrazole-4-sulfonamide; N-(5-chloro-2-{[(2-chlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-[5-chloro-2-({[3-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 30 sulfonamide; N-(5-chloro-2-{[(5-methyl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(5-chloro-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 54 WO 2012/082633 PCT/US2011/064441 N-{5-chloro-2-[(2,3-dihydro-1 -benzofuran-7-ylsulfonyl)amino]phenyl}-1 -benzofuran 2-sulfonamide; N-(5-chloro-2-{[(3-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5 N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-indole-7 sulfonamide; N-{5-chloro-2-[(methylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3,4-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 10 N-{2-[(biphenyl-2-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methylfuran-2-sulfonamide; N-(4,5-dichloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-4,5-d ichlorophenyl)th iophene-2 15 sulfonamide; N-{4,5-dichloro-2-[(phenylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methylbenzoate; N-{4,5-dichloro-2-[(5,6,7,8-tetrahydronaphthalen-2 20 ylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(2-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-2,3-dioxoindoline-5 sulfonamide; N-(5-chloro-2-{[(5-methyl-2-furyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 25 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-(4,5-dichloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; methyl 3-[({4,5-dichloro-2-[(2 30 thienylsulfonyl)amino]phenyl}amino)sulfonyl]thiophene-2-carboxylate; N-(4,5-dichloro-2-{[(2,4,5-trifluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-2-sulfonamide; 55 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}thiophene-2 sulfonamide; 5 N-(5-chloro-2-{[(2,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{5-chloro-2-[(2-furylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2,3-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 10 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzothiazole-6 sulfonamide; N-(4,5-dichloro-2-{[(4-chloro-2,5-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoate; 15 N-(4,5-dichloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-1 -methyl 1 H-pyrrole-2-carboxylate; N-(5-chloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3-benzodioxole-5 sulfonamide; N-{5-chloro-2-[(isobutylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-2 25 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-8-sulfonamide; N-(5-chloro-2-{[(3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(4,5-dichloro-2-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 30 sulfonamide; N-(4,5-dichloro-2-{[(2,4-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-6-sulfonamide; 56 WO 2012/082633 PCT/US2011/064441 N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}am ino)pyridin-2-yl]th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]am ino}phenyl)th iophene 2-sulfonamide; 5 N-(5-chloro-2-{[(2-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5,6-dichloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3 sulfonamide; N-(4,5-dichloro-2-{[(3-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 10 N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 methylphenyl]thiophene-2-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-imidazole-4 sulfonamide; methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 15 chlorophenyl}amino)sulfonyl]thiophene-2-carboxylate; N-(4,5-dichloro-2-{[(4-chloro-2-fluoro-5 methylphenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethyl-1 H-pyrazole 4-sulfonamide; 20 6-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; N-[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene 2-sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -methyl-1 H imidazole-4-sulfonamide; 25 N-(2-{[(3-acetylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-pyrazole-3 sulfonamide; N-{5-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{4-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 30 N-(4,5-dichloro-2-{[(3-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 57 WO 2012/082633 PCT/US2011/064441 N-(4,5-d ichloro-2-{[(2-fluorophenyl)sulfonyl]am ino}phenyl)th iophene-2-sulfonam ide; N-[4,5-dichloro-2-({[4-fluoro-3 (trifluoromethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2-sulfonam ide; N-(4,5-d ichloro-2-{[(4-fluorophenyl)sulfonyl]am ino}phenyl)th iophene-2-sulfonam ide; 5 N,N'-1,2-phenylenedithiophene-2-sulfonamide; N-[4,5-dichloro-2-({[3-(d ifluoromethoxy)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-chloro-4-fluorophenyl)sulfonyl]am ino}phenyl)thiophene-2 sulfonamide; 10 N-(4,5-dichloro-2-{[(3-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{4,5-d ichloro-2-[(3-th ienylsulfonyl)amino]phenyl}th iophene-2-sulfonam ide; N-(4,5-d ichloro-2-{[(3-chloro-4-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(4-chloro-3-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 15 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-3 sulfonamide; 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-8-sulfonamide; N-(4,5-dichloro-2-{[(3,5-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 20 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-3-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-5-sulfonamide; N-(4,5-dichloro-2-{[(3,4-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-l -benzofuran-7 sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 methylphenyl]pyridine-3-sulfonamide; N-(4,5-dichloro-2-{[(2-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 30 N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 1-methyl-1 H-imidazole-4-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-methoxypyridine-3 sulfonamide; 58 WO 2012/082633 PCT/US2011/064441 N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-5-methylthiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-2,3-dihydro-1,4-benzodioxine-6 sulfonamide; 5 N-(4,5-dichloro-2-{[(2,3-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(2-chloro-4-fluorophenyl)sulfonyl]am ino}phenyl)thiophene-2 sulfonamide; 10 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-l-methyl-1 H-indole-5 sulfonamide; N-(4,5-d ichloro-2-{[(2,5-dichloro-3-th ienyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide. More preferred compounds of the invention are: 15 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}thiophene-2 sulfonamide; 6-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]th iophene-2-carboxylate; 20 methyl 3-[({4,5-dichloro-2-[(2 thienylsulfonyl)am ino] phenyl}am ino)sulfonyl]th iophene-2-carboxylate; N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-4,5-d ichlorophenyl)th iophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}pheny)thiophene-2 25 sulfonamide; N-(4,5-dichloro-2-{[(2-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-(4,5-dichloro-2-{[(2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-(4,5-dichloro-2-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 30 N-(4,5-dichloro-2-{[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]amino}phenyl)thiophene 2-sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 59 WO 2012/082633 PCT/US2011/064441 N-(4,5-d ichloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]am ino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(4-fluorophenyl)sulfonyl]am ino}phenyl)th iophene-2-sulfonam ide; N-(5-chloro-2-{[(2,6-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 5 sulfonamide; N-(5-chloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,4-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 10 N-(5-chloro-2-{[(5-methyl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 15 sulfonamide; N-[4,5-dichloro-2-({[4-fluoro-3 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-imidazole-4 sulfonamide; 20 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-pyrazole-3 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethyl-1 H-pyrazole 4-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5-chloro-1,3-dimethyl-1 H 25 pyrazole-4-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-2,3-dioxoindoline-5 30 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methylfuran-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-2-sulfonamide; N-{4-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{5-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide. 60 WO 2012/082633 PCT/US2011/064441 Some compounds of Formula I and some of their intermediates have at least one stereogenic center in their structure. This stereogenic center may be present in an R or S configuration, said R and S notation is used in correspondence with the rules described in Pure Appli. Chem. (1976), 45, 11-13. 5 The term "pharmaceutically acceptable salts" refers to salts or complexes that retain the desired biological activity of the above identified compounds and exhibit minimal or no undesired toxicological effects. The "pharmaceutically acceptable salts" according to the invention include therapeutically active, non-toxic base or acid salt forms, which the compounds of Formula I are able to form. 10 The acid addition salt form of a compound of Formula I that occurs in its free form as a base can be obtained by treating the free base with an appropriate acid such as an inorganic acid, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like; or an organic acid such as for example, acetic, hydroxyacetic, propanoic, lactic, pyruvic, malonic, fumaric acid, 15 maleic acid, oxalic acid, tartaric acid, succinic acid, malic acid, ascorbic acid, benzoic acid, tannic acid, pamoic acid, citric, methylsulfonic, ethanesulfonic, benzenesulfonic, formic and the like (Handbook of Pharmaceutical Salts, P.Heinrich Stahal& Camille G. Wermuth (Eds), Verlag Helvetica Chemica Acta- Zorich, 2002, 329-345). 20 The base addition salt form of a compound of Formula I that occurs in its acid form can be obtained by treating the acid with an appropriate base such as an inorganic base, for example, sodium hydroxide, magnesium hydroxide, potassium hydroxide, Calcium hydroxide, ammonia and the like; or an organic base such as for example, L-Arginine, ethanolamine, betaine, benzathine, morpholine and the like. 25 (Handbook of Pharmaceutical Salts, P.Heinrich Stahal& Camille G. Wermuth (Eds), Verlag Helvetica Chemica Acta- ZOrich, 2002, 329-345). Compounds of Formula I and their salts can be in the form of a solvate, which is included within the scope of the present invention. Such solvates include for example hydrates, alcoholates and the like. 30 With respect to the present invention reference to a compound or compounds, is intended to encompass that compound in each of its possible isomeric forms and mixtures thereof unless the particular isomeric form is referred to specifically. 61 WO 2012/082633 PCT/US2011/064441 Compounds according to the present invention may exist in different polymorphic forms. Although not explicitly indicated in the above formula, such forms are intended to be included within the scope of the present invention. The compounds of the invention are indicated for use in treating or 5 preventing conditions in which there is likely to be a component involving the chemokine receptors. In another embodiment, there are provided pharmaceutical compositions including at least one compound of the invention in a pharmaceutically acceptable carrier. 10 In a further embodiment of the invention, there are provided methods for treating disorders associated with modulation of chemokine receptors. Such methods can be performed, for example, by administering to a subject in need thereof a pharmaceutical composition containing a therapeutically effective amount of at least one compound of the invention. 15 These compounds are useful for the treatment of mammals, including humans, with a range of conditions and diseases that are alleviated by CCR modulation. Therapeutic utilities of CCR modulators are skin inflammatory diseases and conditions, including, but are not limited to: rosacea (dilation of the blood vessels 20 just under the skin), sunburn, chronic sun damage, discreet erythemas, psoriasis, atopic dermatitis, menopause-associated hot flashes, hot flashes resulting from orchiectomyatopic dermatitis, photoaging, seborrheic dermatitis, acne, allergic dermatitis, irritant dermatitis, telangiectasia (dilations of previously existing small blood vessels ) of the face, rhinophyma (hypertrophy of the nose with follicular 25 dilation), red bulbous nose, acne-like skin eruptions (may ooze or crust), burning or stinging sensation of the face, irritated and bloodshot and watery eyes, cutaneous hyperactivity with dilation of blood vessels of the skin, Lyell's syndrome, Stevens Johnson syndrome, erythema multiforme minor, erythema multiforme major and other inflammatory skin diseases, actinic keratoses, arsenic keratoses, inflammatory 30 and non-inflammatory acne, ichthyoses and other keratinization and hyperproliferative disorders of the skin, eczema, wound healing. Therapeutic utilities of CCR modulators are ocular inflammatory diseases including, but not limited to, uveitis, dry eye, Keratitis, allergic eye disease and conditions affecting the posterior part of the eye, such as maculopathies and retinal 62 WO 2012/082633 PCT/US2011/064441 degeneration including non-exudative age related macular degeneration, exudative age related macular degeneration, choroidal neovascularization, diabetic retinopathy, acute macular neuroretinopathy, central serous chorioretinopathy, cystoid macular edema, and diabetic macular edema; uveitis, retinitis, and 5 choroiditis such as acute multifocal placoid pigment epitheliopathy, Behcet's disease, birdshot retinochoroidopathy, infectious (syphilis, lyme, tuberculosis, toxoplasmosis), intermediate uveitis (pars planitis), multifocal choroiditis, multiple evanescent white dot syndrome (mewds), ocular sarcoidosis, posterior scleritis, serpiginous choroiditis, subretinal fibrosis and uveitis syndrome, Vogt-Koyanagi-and 10 Harada syndrome; vasuclar diseases/ exudative diseases such as retinal arterial occlusive disease, central retinal vein occlusion, disseminated intravascular coagulopathy, branch retinal vein occlusion, hypertensive fundus changes, ocular ischemic syndrome, retinal arterial microaneurysms, Coat's disease, parafoveal telangiectasis, hemi-retinal vein occlusion, papillophlebitis, central retinal artery 15 occlusion, branch retinal artery occlusion, carotid artery disease (CAD), frosted branch angiitis, sickle cell retinopathy and other hemoglobinopathies, angioid streaks, familial exudative vitreoretinopathy, and Eales disease; traumatic/ surgical conditions such as sympathetic ophthalmia, uveitic retinal disease, retinal detachment, trauma, conditions caused by laser, conditions caused by 20 photodynamic therapy, photocoagulation, hypoperfusion during surgery, radiation retinopathy, and bone marrow transplant retinopathy; proliferative disorders such as proliferative vitreal retinopathy and epiretinal membranes, and proliferative diabetic retinopathy; infectious disorders such as ocular histoplasmosis, ocular toxocariasis, presumed ocular histoplasmosis syndrome (POHS), endophthalmitis, 25 toxoplasmosis, retinal diseases associated with HIV infection, choroidal disease associate with HIV infection, uveitic disease associate with HIV infection, viral retinitis, acute retinal necrosis, progressive outer retinal necrosis, fungal retinal diseases, ocular syphilis, ocular tuberculosis, diffuse unilateral subacute neuroretinitis, and myiasis; genetic disorders such as retinitis pigmentosa, systemic 30 disorders with accosiated retinal dystrophies, congenital stationary night blindness, cone dystrophies, Stargardt's disease and fundus flavimaculatus, Best's disease, pattern dystrophy of the retinal pigmented epithelium, X-linked retinoschisis, Sorsby's fundus dystrophy, benign concentric maculopathy, Bietti's crystalline dystrophy, and pseudoxanthoma elasticum; retinal tears/ holes such as retinal 63 WO 2012/082633 PCT/US2011/064441 detachment, macular hole, and giant retinal tear; tumors such as retinal disease associated with tumors, congenital hypertrophy of the retinal pigmented epithelium, posterior uveal melanoma, choroidal hemangioma, choroidal osteoma, choroidal metastasis, combined hamartoma of the retina and retinal pigmented epithelium, 5 retinoblastoma, vasoproliferative tumors of the ocular fundus, retinal astrocytoma, and intraocular lymphoid tumors; and miscellaneous other diseases affecting the posterior part of the eye such as punctate inner choroidopathy, acute posterior multifocal placoid pigment epitheliopathy, myopic retinal degeneration, and acute retinal pigement epitheliitis. . 10 In still another embodiment of the invention, there are provided methods for treating disorders associated with modulation of chemokine receptors. Such methods can be performed, for example, by administering to a subject in need thereof a therapeutically effective amount of at least one compound of the invention, or any combination thereof, or pharmaceutically acceptable salts, hydrates, 15 solvates, crystal forms and individual isomers, enantiomers, and diastereomers thereof. The present invention concerns the use of a compound of Formula I or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of ocular inflammatory diseases including, but not limited to, uveitis, 20 dry eye, Keratitis, allergic eye disease and conditions affecting the posterior part of the eye, such as maculopathies and retinal degeneration including non-exudative age related macular degeneration, exudative age related macular degeneration, choroidal neovascularization, diabetic retinopathy, acute macular neuroretinopathy, central serous chorioretinopathy, cystoid macular edema, and diabetic macular 25 edema; uveitis, retinitis, and choroiditis such as acute multifocal placoid pigment epitheliopathy, Behcet's disease, birdshot retinochoroidopathy, infectious (syphilis, lyme, tuberculosis, toxoplasmosis), intermediate uveitis (pars planitis), multifocal choroiditis, multiple evanescent white dot syndrome (mewds), ocular sarcoidosis, posterior scleritis, serpiginous choroiditis, subretinal fibrosis and uveitis syndrome, 30 Vogt-Koyanagi-and Harada syndrome; vasuclar diseases/ exudative diseases such as retinal arterial occlusive disease, central retinal vein occlusion, disseminated intravascular coagulopathy, branch retinal vein occlusion, hypertensive fundus changes, ocular ischemic syndrome, retinal arterial microaneurysms, Coat's disease, parafoveal telangiectasis, hemi-retinal vein occlusion, papillophlebitis, 64 WO 2012/082633 PCT/US2011/064441 central retinal artery occlusion, branch retinal artery occlusion, carotid artery disease (CAD), frosted branch angiitis, sickle cell retinopathy and other hemoglobinopathies, angioid streaks, familial exudative vitreoretinopathy, and Eales disease; traumatic/ surgical conditions such as sympathetic ophthalmia, uveitic 5 retinal disease, retinal detachment, trauma, conditions caused by laser, conditions caused by photodynamic therapy, photocoagulation, hypoperfusion during surgery, radiation retinopathy, and bone marrow transplant retinopathy; proliferative disorders such as proliferative vitreal retinopathy and epiretinal membranes, and proliferative diabetic retinopathy; infectious disorders such as ocular histoplasmosis, 10 ocular toxocariasis, presumed ocular histoplasmosis syndrome (POHS), endophthalmitis, toxoplasmosis, retinal diseases associated with HIV infection, choroidal disease associate with HIV infection, uveitic disease associate with HIV infection, viral retinitis, acute retinal necrosis, progressive outer retinal necrosis, fungal retinal diseases, ocular syphilis, ocular tuberculosis, diffuse unilateral 15 subacute neuroretinitis, and myiasis; genetic disorders such as retinitis pigmentosa, systemic disorders with accosiated retinal dystrophies, congenital stationary night blindness, cone dystrophies, Stargardt's disease and fundus flavimaculatus, Best's disease, pattern dystrophy of the retinal pigmented epithelium, X-linked retinoschisis, Sorsby's fundus dystrophy, benign concentric maculopathy, Bietti's 20 crystalline dystrophy, and pseudoxanthoma elasticum; retinal tears/ holes such as retinal detachment, macular hole, and giant retinal tear; tumors such as retinal disease associated with tumors, congenital hypertrophy of the retinal pigmented epithelium, posterior uveal melanoma, choroidal hemangioma, choroidal osteoma, choroidal metastasis, combined hamartoma of the retina and retinal pigmented 25 epithelium, retinoblastoma, vasoproliferative tumors of the ocular fundus, retinal astrocytoma, and intraocular lymphoid tumors; and miscellaneous other diseases affecting the posterior part of the eye such as punctate inner choroidopathy, acute posterior multifocal placoid pigment epitheliopathy, myopic retinal degeneration, and acute retinal pigement epitheliitis. 30 The actual amount of the compound to be administered in any given case will be determined by a physician taking into account the relevant circumstances, such as the severity of the condition, the age and weight of the patient, the patient's general physical condition, the cause of the condition, and the route of administration. 65 WO 2012/082633 PCT/US2011/064441 The patient will be administered the compound orally in any acceptable form, such as a tablet, liquid, capsule, powder and the like, or other routes may be desirable or necessary, particularly if the patient suffers from nausea. Such other routes may include, without exception, transdermal, parenteral, subcutaneous, 5 intranasal, via an implant stent, intrathecal, intravitreal, topical to the eye, back to the eye, intramuscular, intravenous, and intrarectal modes of delivery. Additionally, the formulations may be designed to delay release of the active compound over a given period of time, or to carefully control the amount of drug released at a given time during the course of therapy. 10 In another embodiment of the invention, there are provided pharmaceutical compositions including at least one compound of the invention in a pharmaceutically acceptable carrier thereof. The phrase "pharmaceutically acceptable" means the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. 15 Pharmaceutical compositions of the present invention can be used in the form of a solid, a solution, an emulsion, a dispersion, a patch, a micelle, a liposome, and the like, wherein the resulting composition contains one or more compounds of the present invention, as an active ingredient, in admixture with an organic or inorganic carrier or excipient suitable for enteral or parenteral applications. 20 Invention compounds may be combined, for example, with the usual non-toxic, pharmaceutically acceptable carriers for tablets, pellets, capsules, suppositories, solutions, emulsions, suspensions, and any other form suitable for use. The carriers which can be used include glucose, lactose, gum acacia, gelatin, mannitol, starch paste, magnesium trisilicate, talc, corn starch, keratin, colloidal silica, potato 25 starch, urea, medium chain length triglycerides, dextrans, and other carriers suitable for use in manufacturing preparations, in solid, semisolid, or liquid form. In addition auxiliary, stabilizing, thickening and coloring agents and perfumes may be used. Invention compounds are included in the pharmaceutical composition in an amount sufficient to produce the desired effect upon the process or disease condition. 30 Pharmaceutical compositions containing invention compounds may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Compositions intended for oral use may be prepared according to any method known in the art for the manufacture of pharmaceutical compositions 66 WO 2012/082633 PCT/US2011/064441 and such compositions may contain one or more agents selected from the group consisting of a sweetening agent such as sucrose, lactose, or saccharin, flavoring agents such as peppermint, oil of wintergreen or cherry, coloring agents and preserving agents in order to provide pharmaceutically elegant and palatable 5 preparations. Tablets containing invention compounds in admixture with non-toxic pharmaceutically acceptable excipients may also be manufactured by known methods. The excipients used may be, for example, (1) inert diluents such as calcium carbonate, lactose, calcium phosphate or sodium phosphate; (2) granulating and disintegrating agents such as corn starch, potato starch or alginic 10 acid; (3) binding agents such as gum tragacanth, corn starch, gelatin or acacia, and (4) lubricating agents such as magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as 15 glyceryl monostearate or glyceryl distearate may be employed. In some cases, formulations for oral use may be in the form of hard gelatin capsules wherein the invention compounds are mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin. They may also be in the form of soft gelatin capsules wherein the invention compounds are mixed with water 20 or an oil medium, for example, peanut oil, liquid paraffin or olive oil. The pharmaceutical compositions may be in the form of a sterile injectable suspension. This suspension may be formulated according to known methods using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a 25 non-toxic parenterally-acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed including synthetic mono- or diglycerides, fatty acids (including oleic acid), naturally occurring vegetable oils like sesame oil, coconut oil, peanut oil, cottonseed oil, etc., 30 or synthetic fatty vehicles like ethyl oleate or the like. Buffers, preservatives, antioxidants, and the like can be incorporated as required. Invention compounds may also be administered in the form of suppositories for rectal administration of the drug. These compositions may be prepared by mixing the invention compounds with a suitable non-irritating excipient, such as 67 WO 2012/082633 PCT/US2011/064441 cocoa butter, synthetic glyceride esters of polyethylene glycols, which are solid at ordinary temperatures, but liquefy and/or dissolve in the rectal cavity to release the drug. Invention compounds and their pharmaceutically-acceptable salts may be 5 administered through different routes, including but not limited to topical eye drops, direct injection, application at the back of the eye or formulations that may further enhance the long duration of actions such as a slow releasing pellet, suspension, gel, or sustained delivery devices such as any suitable drug delivery system (DDS) known in the art. While topical administration is preferred, this compound may also 10 be used in an intraocular implant as described in U.S. U.S. Patent 7,931,909. Since individual subjects may present a wide variation in severity of symptoms and each drug has its unique therapeutic characteristics, the precise mode of administration and dosage employed for each subject is left to the discretion of the practitioner. 15 The compounds and pharmaceutical compositions described herein are useful as medicaments in mammals, including humans, for treatment of diseases and/or alleviations of conditions which are responsive to treatment by agonists or functional antagonists of chemokine receptors. Thus, in further embodiments of the invention, there are provided methods for treating a disorder associated with 20 modulation of chemokine receptors. Such methods can be performed, for example, by administering to a subject in need thereof a pharmaceutical composition containing a therapeutically effective amount of at least one invention compound. As used herein, the term "therapeutically effective amount" means the amount of the pharmaceutical composition that will elicit the biological or medical response of 25 a subject in need thereof that is being sought by the researcher, veterinarian, medical doctor or other clinician. In some embodiments, the subject in need thereof is a mammal. In some embodiments, the mammal is human. The present invention concerns also processes for preparing the compounds of Formula 1. The compounds of formula I according to the invention can be 30 prepared analogously to conventional methods as understood by the person skilled in the art of synthetic organic chemistry. The synthetic schemes set forth below, illustrate how compounds according to the invention can be made. Those skilled in the art will be able to routinely modify and/or adapt Scheme 1 or Scheme 2 to synthesize any compound of the invention covered by Formula I. 68 WO 2012/082633 PCT/US2011/064441 The following abbreviations are used in the general schemes and in the specific examples:
NH
4
HCO
3 ammonium bicarbonate
CH
3 CN acetonitrile 5 CH 2
CI
2 dichloromethane DMF N,N-dimethylformamide NaOH sodium hydroxide MeOH methanol
CD
3 0D deuterated methanol 10 NH 3 ammonia HCI hydrochloric acid Na 2
SO
4 sodium sulfate NaHCO 3 sodium bicarbonate EtOH ethanol 15 MgSO 4 magnesium sulfate EtOAc ethyl acetate CDCl 3 deuterated chloroform CHCl 3 chloroform DMSO-d 6 deuterated dimethyl sulfoxide 20 Et 3 N triethylamine DIPEA N,N-Diisopropylethylamine TFA trifluoroacetic acid THF tetrahydrofuran NaH sodium hydride 25 HOAc acetic acid DMAP 4-dimethylaminopyridine
NH
4 CI ammonium chloride Et 2 O diethylether MeLi methylithium 30 H 2 hydrogen (gas) Pd-C palladium on carbon Zn zinc Scheme 1 69 WO 2012/082633 PCT/US2011/064441 wherein R 6 is R6
R
5 1 O=S=0
R'
5 R I I R R 15 O=S=O O=S=0 C' 1
AR
15
NH
2 .. R4 - R RCI 15 N, 1 'R17 N ||1 R3 R1 R || Method A R17 NH 2 i R4 6or NR17 NH 2 Method B Rs or Formula I Intermediate A Method C iii
R
5 I SR6 O=S=01 R6 O =S=O O=S=0 R3 5 N 0 3'R 1 5 N v, v2 11 Method D R17 N R or R17 NH 2 Method E O=S=O Intermediate B Intermediate C i: 2-thiophenesulfonyl chloride, CH 2 Cl 2 , pyridine, OC to rt, 67%; ii: sulfonyl chloride, pyridine, 100 C (30 min) or rt (2 h), ca. 30% on average; iii: 1-chloromethyl ethyl ether, NaH, THF, 0*C, 63%; iv: aromatic sulfonyl chlorides: MeLi, THF, OC, then sulfonyl chloride, OC to rt, ca. 30%; aliphatic sulfonyl chlorides: Et 3 N, DMAP, CHCl 3 , acetone, 50'C, 10-48%; v: 4M HCI/dioxane, EtOH, rt, ca. 60-90%; Scheme 2 wherein R 6 is 5 70 WO 2012/082633 PCT/US2011/064441 O=SO ~SO O S O
R
15 NH C02R 5 H2R1 5 II.~R6 N ~R R6 I II I 3 R15 NO 2 i 151-1 Intermediate D Intermediate E O S O R 15 N R CII , 1 R O=S=O Formula I iNaH, dry DMF, -10CC, 10 min, then 1-benzofuran-2-sulfonyl chloride in DMF, 10 min addition, -10oC, 30 min, 88%; ii: Zn, sat. aq. NH 4 CI, THE, MeOH, r.t., 20 min, 69%; iii: Sulfonyl chloride, pyridine, 10000 (30 min) or r.t. (2 h), ca. 38% on average Sulfonamide Intermediate A was prepared starting with an appropriately substituted phenylene diamine. Sulfonamide Intermediate 0 was prepared starting with an appropriately substituted 2-nitroaniline. Reduction of Intermediate 0 with 5 zinc dust and saturated aqueous ammonium chloride solution in THF and methanol afforded Intermediate E type. The bis-sulfonamide of Formula I was prepared from Intermediate A or Intermediate E in pyridine at either 10000 (Method A for aromatic sulfonyl chlorides; or Method B with modified workup for aromatic sulfonyl chlorides containing a carboxylic acid group), or at room temperature (rt) (Method 10 C). For aliphatic sulfonyl chloride and for aromatic sulfonyl chlorides that failed using method A, B, or C, the synthesis was modified via Intermediate B and Intermediate C. Protection of the sulfonamide nitrogen of Intermediate A using 1 chloromethyl ethyl ether afforded hemiaminal ether Intermediate B. 71 WO 2012/082633 PCT/US2011/064441 Deprotonation of Intermediate B with methyl lithium (MeLi) and subsequent reaction with aromatic sulfonyl chlorides afforded compounds of type Intermediate C, which were deprotected to bis-sulfonamides of Formula I using 4M hydrochloric acid(HCI)/dioxane in the presence of ethanol (both steps combined: 5 Method D). Reactions of Intermediate B with aliphatic sulfonyl chlorides were performed in the presence of triethylamine and 4- dimethylaminopyridine (DMAP) in chloroform(CHCI 3 )/acetone at 500C afforded compounds of type Intermediate C, which were deprotected to bis-sulfonamides of Formula I using 4M hydrochloric 10 acid(HCI)/dioxane in the presence of ethanol (both steps combined: Method E). DETAILED DESCRIPTION OF THE INVENTION It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention claimed. As used herein, the use of the singular includes 15 the plural unless specifically stated otherwise. It will be readily apparent to those skilled in the art that some of the compounds of the invention may contain one or more asymmetric centers, such that the compounds may exist in enantiomeric as well as in diastereomeric forms. Unless it is specifically noted otherwise, the scope of the present invention includes 20 all enantiomers, diastereomers and racemic mixtures. Some of the compounds of the invention may form salts with pharmaceutically acceptable acids or bases, and such pharmaceutically acceptable salts of the compounds described herein are also within the scope of the invention. The present invention includes all pharmaceutically acceptable isotopically 25 enriched compounds. Any compound of the invention may contain one or more isotopic atoms enriched or different than the natural ratio such as deuterium 2 H (or D) in place of protium 1 H (or H) or use of 13 C enriched material in place of 12C and the like. Similar substitutions can be employed for N, 0 and S. The use of isotopes may assist in analytical as well as therapeutic aspects of the invention. For 30 example, use of deuterium may increase the in vivo half-life by altering the metabolism (rate) of the compounds of the invention. These compounds can be prepared in accord with the preparations described by use of isotopically enriched reagents. 72 WO 2012/082633 PCT/US2011/064441 As will be evident to those skilled in the art, individual isomeric forms can be obtained by separation of mixtures thereof in conventional manner. For example, in the case of diasteroisomeric isomers, chromatographic separation may be employed. 5 The IUPAC names of the compounds mentioned in the examples were generated with ACD version 8 and some intermediates' and reagents' names used in the examples were generated with software such as Chem Bio Draw Ultra version 12.0 or Auto Nom 2000 from MDL ISIS Draw 2.5 SP1. In general, characterization of the compounds is performed by nuclear 10 magnetic resonance and/or mass spectrometry. NMR spectra, recorded on Bruker Avance 300, 1 H-NMR (300 MHz) in the indicated solvent at ambient temperature; chemical shifts in ppm, coupling constants in Hz. HPLC-MS: HPLC-System: Agilent 1100 Series, MS: Thermo Dionex Surveyor MSQ Plus. Column GeminiNX C18, 3 pm, 2.1x50 mm, gradient: 97% A (acidic: 0.1% TFA in water; basic: 1mM NH 4
HCO
3 15 in water pH 10) and 3% B (acidic: 0.085% TFA in CH 3 CN; basic: CH 3 CN) for 0.1 min, then in 2.1 min to 3% A and 97% B, then 3%A and 97%B for 0.3 min (flow: 0.8 ml/min); Or column Ascentis express C18, 2.7 pm, 3x50 mm, gradient: 97% A (acidic: 0.1% TFA in water; basic: 1mM NH 4
(CO
3
)
2 in water pH 10) and 3% B (acidic: 0.085% TFA in CH 3 CN; basic: CH 3 CN) for 0.05 min, then in 2.9 min to 3% A 20 and 97% B, then 3%A and 97%B for 0.2 min (flow: 1.3 ml/min); retention times tR in [min]; UV detection at 254 and 220 nm; ionization method as indicated. All the reagents, solvents, catalysts for which the synthesis is not described are purchased from chemical vendors such as Sigma Aldrich, Fluka, Bio-Blocks, Combi-blocks, TCI, VWR, Lancaster, Oakwood, Trans World Chemical, Alfa, Fisher, 25 Maybridge, Frontier, Matrix, Ukrorgsynth, Toronto, Ryan Scientific, SiliCycle, Anaspec, Syn Chem, Chem-Impex, MIC-scientific, Ltd; however some known intermediates, were prepared according to published procedures. Solvents were purchased from commercial sources in appropriate quality and used as received. Air and/or moisture-sensitive reactions were run under an argon or nitrogen 30 atmosphere. Usually the compounds of the invention were purified by chromatography: TLC: Merck (silica gel 60 F 254 , 0.25 mm); Flash chromatography: Fluka silica gel 60 (0.04-0.063 mm) and Interchim Puriflash IR 60 silica gel (0.04-0.063 mm); 73 WO 2012/082633 PCT/US2011/064441 MPLC Normal Phase: Solvent system hexane (A) / EtOAc (B), column D: YMC*Gel Silica SL06S50 (0.006-50 pm), 60 x 200 mm, flow 175 ml/min, program 3 (start with 7% B, then in 12 min 100% B, then 100% B for 5 min), program 7 (start with 25% B, then in 12 min 100% B, then 100% B for 5.5 min); 5 Normal Phase Preparative HPLC: Macherey-Nagel VP1 00/21 Nucleosil 50A 10 tm, hexane/EtOAc/MeOH gradient. Reverse Phase Preparative HPLC: Waters Xbridge C18 150x30 mm, 5 tm or Phenomenex GeminiNX C18 axia pack 100x30 mm, 5 tm, water/CH 3 CN gradient with 0.1% TFA or 10 mM NH 4
HCO
3 (pH 10). 10 The following examples are for illustrative purposes only and are not intended, nor should they be construed as limiting the invention in any manner. Those skilled in the art will appreciate that variations and modifications of the following examples can be made without exceeding the spirit or scope of the invention. 15 SYNTHESIS OF BIS-SULFONAMIDES OF FORMULA I METHOD A Method A is applied when R 5 does not contain a carboxylic acid group. To a solution of Intermediate A (50 mg, 0.155 mmol) in pyridine (1 ml) was added 20 sulfonyl chloride (1.5 eq.) at room temp. The screw cap tube containing the mixture was quickly transferred in a 100 C hot heating block, the mixture was stirred at 100 C for 30 min. If the reaction failed according to TLC analysis (or HPLC analysis in cases of doubts), Method C was applied. If TLC analysis (or HPLC analysis in cases of doubt) showed the presence of major amount of starting material, 25 additional sulfonyl chloride (1.5 eq.) was added and stirring at 100 C was continued for another 30 min. Half-saturated aq. NaHCO 3 solution was added at room temperature and extraction with CH 2
CI
2 followed. The organic layer was filtered through a pad of MgSO 4 and silica gel, the pad was rinsed with CH 2 CI2/MeOH 9:1 and the filtrate was 30 concentrated. Purification by preparative normal phase HPLC (oversized column: Machery-Nagel VP 150/32 Nucleosil 50-10, hexane/EtOAc/MeOH gradient) afforded the compound of Formula I. If further purification was required, a wash using Et 2 O or additional purification by reverse phase preparative HPLC, or 74 WO 2012/082633 PCT/US2011/064441 dependending on the nature of the material, a wash procedure using Et 2 0/CH 2
CI
2 was performed. METHOD B 5 Method B is applied when R 5 contains a carboxylic acid group. The reaction was performed as described in Method A, the workup was modified: Half-saturated aq. NaHCO 3 solution was added at room temperature and extraction with CH 2
CI
2 followed. The pH was adjusted to 2 by adding adding 4M aq. HCI solution to the aqueous layer. The mixture was extracted with CH 2
CI
2 the product is 10 formed as immiscible oil. In this case, the aq. layer was removed, MeOH was added in order to dissolve the oil into the organic layer, the organic layer was filtered through a pad of MgSO 4 and silica gel, the pad was rinsed with CH 2 CI2/ MeOH 8:2 and the filtrate was concentrated. Purification by preparative reverse phase HPLC (acidic mobile phase) afforded the compound of Formula I. If further purification 15 was needed, a wash procedure using Et 2 O (ultrasound bath) followed or additional purification was performed by reverse phase preparative HPLC (acidic mobile phase). METHOD C To a solution of Intermediate A (80 mg, 0.248 mmol) in pyridine (1 ml) was 20 added sulfonyl chloride (1.5 eq.) at room temperature (screw cap tube) The mixture was stirred at room temperature for 2 h. If the reaction failed according to TLC analysis (or HPLC analysis in cases of doubts), Method D was applied. If TLC analysis (or HPLC analysis in cases of doubt) showed the presence of a major amount of starting material, additional sulfonyl chloride (1.5 eq.) was added and 25 stirring at room temp. was continued for 1 h. The workup and purification were performed as described in Method A. METHOD D Deprotonation of Intermediate B with methyl lithium and subsequent reaction with aromatic sulfonyl chlorides afforded Intermediate C type compounds, 30 which were deprotected to give the compound of Formula I using 4M Hydrochloric acid/dioxane in the presence of ethanol. METHOD E 75 WO 2012/082633 PCT/US2011/064441 Method E is applied when R 5 is an aliphatic group. Reactions of Intermediate B with aliphatic sulfonyl chlorides were performed in the presence of triethylamine and 4- dimethylaminopyridine (DMAP) in chloroform(CHCI 3 )/acetone at 500C to afford Intermediate C compounds, which 5 were deprotected to give the compound of Formula I using 4M Hydrochloric acid/dioxane in the presence of ethanol. Preparation of intermediates Intermediate 1 N-(2-amino-4,5-dichlorophenyl)thiophene-2-sulfonamide o=S S CI NH 10 C NH 2 To an ice cold solution of 4,5-dichloro-o-phenylenediamine (CAS RN: 5348 42-5), (15.78 g, 89.14 mmol) in CH 2
CI
2 (185 ml) and pyridine (45 ml) was added a solution of 2-thiophenesulfonyl chloride (17.1 g, 93.62 mmol, 1.05 eq.) in CH 2
CI
2 (40 ml). The mixture (black solution) was stirred and allowed to warm to room 15 temperature overnight (without removal of the cooling bath), then added to EtOAc and washed with sat. aq. NaHCO 3 solution. The aq. layer was extracted 2x with EtOAc, the combined organic layers were dried (Na 2
SO
4 ) and concentrated. The crude product was combined with the crude product of an analogously performed 10 g scale attempt, chromatography on silica gel (hexane/EtOAc 8:2 to 6:4, 20 chromatography was repeated with mixed fractions using the same eluent) and afforded Intermediate 1 (31.5 g, 67%) as brown solid.
C
10
H
8 Cl 2
N
2 0 2
S
2 (323.22). MS (ESI*): 325/323 [M+H]*. 1 H-NMR (DMSO-d 6 ): 5 ppm 9.8-9.5 (br. signal, 1H); 7.95 (dd, J = 1.4, 5.0, 1H); 7.50 (dd, J = 1.4, 3.7, 1H); 7.16 (dd, J = 3.8, 5.0, 1 H); 6.87, 6.85 (2s, 2x1 H); 5.5-5.25 (br. s, 2H). 25 Intermediate 2 N-(2-amino-4,5-dichlorophenyl)-N-(ethoxymethyl)thiophene-2-sulfonamide 76 WO 2012/082633 PCT/US2011/064441 0 S CI N CI
NH
2 To an ice cold solution of Intermediate 1 (3.24 g, 10.02 mmol) in THF (90 ml) and DMF (30 ml) was added NaH (ca. 60% in mineral oil, 0.6 g, ca. 15 mmol, 1.5 eq., gas evolution, brown solution). The mixture was stirred at 00C for 30 min 5 (dark colored after 5 min), then a solution of 1 -chloromethyl ethyl ether (1.02 ml, ca. 1.04 g, 11 mmol, 1.1 eq.) was added dropwise at 00C. The brown, light green mixture was stirred at 00C for 1 h, then sat. aq. NaHCO 3 solution (ca. 10 ml) was added at 00C. The mixture was concentrated (rotary evaporator), water was added and extraction with EtOAc followed. The organic layer was washed with water (2x) 10 and brine, dried (Na 2
SO
4 ) and concentrated. The crude product was adsorbed on silica gel (CH 2 Cl 2 /MeOH), chromatography on silica gel (hexane/acetone 90:10 to 88:12 to 86:14 to 84:16 to 82:18 to 80:20) afforded Intermediate 2 (2.4 g, 63%) as brown solid.
C
13
H
14 Cl 2
N
2 0 3
S
2 (381.30). MS (ESI*): 383/381 [M+H]*. 'H-NMR (DMSO-d 6 ): 5 ppm 15 8.05 (dd, J = 0.5, 4.9, 1 H); 7.65 (dd, J = 0.5, 3.7, 1 H); 7.24 (dd, J = 3.8, 5.0, 1 H); 6.92, 6.72 (2s, 2x1 H); 5.60 (br. s, 2H, exchanged upon treatment with D 2 0); 5.20 5.05 (br. signal, 1 H); 4.78-4.62 (br. signal, 1 H); 3.54 (q, J = 7.0, 2H); 1.09 (t, J = 7.0, 3H). Intermediate 3 20 N-(4,5-dichloro-2-(3-chloro-4-fluorophenylsulfonamido)phenyl)-N (ethoxymethyl) thiophene-2-sulfonamide O o=s S CI N CI NH I~ C Sulfonamide formation according to METHOD D: To an ice cold solution of 25 Intermediate 2 (70 mg, 0.184 mmol) in THF (1 ml) was added dropwise MeLi 77 WO 2012/082633 PCT/US2011/064441 (1.6M in Et 2 0, 0.25 ml, ca. 0.4 mmol, 2.2 eq.). The dark green mixture was stirred at 00C for 15 min, then a solution of an aromatic sulfonyl chloride for example: 3 chloro-4-fluorobenzenesulfonyl chloride (63.1 mg, 0.275 mmol, 1.5 eq.) in THF (1 ml) was added dropwise at 00C. The orange solution was stirred at 00C for 40 min 5 and at room temp. overnight. MeOH was added at room temp. and the mixture was concentrated. Purification by reverse phase preparative HPLC (acidic mobile phase) afforded Intermediate 3 (37 mg, 35%) as light yellow solid. 'H-NMR (DMSO-d 6 ): 5 ppm 10.6-10.35 (br. signal, 1H); 8.14 (dd, J = 2.1, 6.7, 1H); 8.08 (dd, J = 1.3, 5.0, 1 H); 7.94-7.89 (m, 1 H); 7.67 (t, J = 8.9, 1 H); 7.60 (s, 1 H); 7.56 10 (dd, J = 1.3, 3.8, 1 H); 7.23 (dd, J = 3.9, 4.9, 1 H); 6.86 (s, 1 H); 5.4-5.0 (br. signal, 1 H); 4.5-4.1 (br. signal, 1 H); 3.41 (partially hidden, partially resolved q, J = 7.0, 2H); 1.04 (t, J = 7.0, 3H). Intermediate 4 Benzofuran-2-sulfonic acid (5-chloro-2-nitro-phenyl)-amide CI NH 15 NO 2 To a -100C cold yellow solution of 5-chloro-2-nitroaniline (8.00 g, 46.36 mmol) in dry DMF (130 ml) was added sodium hydride 60% (9.27 g, 231.79 mmol) under Ar. The resulting red suspension was stirred at -10 C for 10 minutes. A solution of 1-benzofuran-2-sulfonyl chloride (12.05 g, 55.63 mmol) in dry DMF (50 20 ml) was added dropwise with a dropping funnel at -10 C (10 minutes of addition, exothermic reaction, maximum temperature of addition was OC, 5 ml of DMF to rinse the funnel). The resulting orange suspension was stirred at -10 C for 30 minutes (color changed to brown). The reaction mixture was quenched with half saturated NaHCO 3 solution (400 ml) and the product was extracted five times with 25 EtOAc (1 x 650 ml and 4 x 300 ml). The combined organic layers were dried over Na 2
SO
4 , filtered and the filtrate evaporated to dryness. The crude product was combined with the crude product of an analogously performed 8 g scale attempt to give 61.82 g of an orange oil which was purified by MPLC (crude was dissolved in
CH
2
CI
2 /MeOH, preabsorption on silica gel, column D, program 3, 5 runs) to afford 78 WO 2012/082633 PCT/US2011/064441 Intermediate 4 (28.91 g, 88% yield based on combined starting material) as yellow solid.
C
14
H
9
CIN
2 0 5 S (352.75). HPLC-MS (basic mobile phase, ESI-): tR = 1.31 min, 350.7 [M-H]-. 1 H-NMR (DMSO-d 6 ): 7.70 (ddd, J = 0.6, 1.3, 7.8, 1H); 7.60 (dd, J = 0.8, 8.3, 5 1H); 7.52-7.47 (m, 2H); 7.39 (m, 1H); 7.28 (m, 1H); 7.18 (s, 1H); 6.75 (d, J = 8.3, 1 H). Intermediate 5 Benzofuran-2-sulfonic acid (2-amino-5-chloro-phenyl)-amide 0 0 o=s II CI NH
NH
2 10 To an orange solution of Intermediate 4 (14.41 g, 40.85 mmol) in THF (55 ml) and MeOH (285 ml) was added saturated aqueous NH 4 CI solution (285 ml, precipitation of starting material) and then Zinc (20.03 g, 306.38 mmol) in a cold water bath (200C). The resulting suspension was stirred at room temperature for 20 minutes (color changed from brown to dark green). EtOAc (400 ml) and saturated 15 aqueous NH 4 CI solution (400 ml) were added. The solid in suspension was filtered through a pad of celite and washed with EtOAc (3 x 250 ml) and saturated aqueous
NH
4 CI solution (3 x 200 ml). The filtrate was shaken and the organic layer was collected, dried over Na 2
SO
4 , filtered and evaporated to dryness. The residue was dissolved in CH 2 Cl 2 , filtered through a pad of silica, washed three times with 20 CH 2
CI
2 /MeOH 9/1 and evaporated to dryness. The crude product was combined with the crude product of an analogously performed 14.41 g scale attempt to leave 27.23 g of red foam. The crude foam was dissolved in CH 2
CI
2 /MeOH 99/1 whereupon a solid precipitates. The mixture was evaporated to dryness and re dissolved in a mixture of EtOAc/MeOH. The remaining solid was filtered off. The 25 filtrate was preabsorbed on silica gel and purified by flash chromatography over silica gel eluted with CH 2
CI
2 /MeOH from 99/1 to 97/3 to give 20.25 g of impure brown solid. This product was repurified by MPLC (crude was dissolved in
CH
2
CI
2 /MeOH, preabsorption on silica gel, column D, program 7, 5 runs) to afford Intermediate 5 (18.18 g, 69% yield based on combined starting material) as beige 30 solid. 79 WO 2012/082633 PCT/US2011/064441
C
14
H
1 1
CIN
2 0 3 S (322.76). HPLC-MS (acidic mobile phase, ESI*): tR = 1.93 min, 323/325 [M+H]*. 1 H-NMR (DMSO-d 6 ): 10.7-9.3 (br. signal, ca. 1H); 7.75 (m, 2H); 7.60-7.50 (m, 2H); 7.39 (m, 1 H); 6.96 (dd, J = 2.5, 8.7, 1 H); 6.81 (d, J = 2.5, 1 H); 6.62 (d, J = 8.7, 1H), 6.9-5.4 (br. signal, ca. 2H). 5 Intermediate 6 Benzofuran-2-sulfonic acid (4-chloro-2-nitro-phenyl)-amide 0 O=S I NH CI
NO
2 To a solution of 4-chloro-2-nitroaniline (CAS RN: 89-63-4) (0.52 g, 3.0 mmol) in pyridine (3.0 ml) was added benzofuran-2-sulfonyl chloride (0.65 g, 3.0 mmol) 10 and the mixture was stirred at room temperature for 64 h. More benzofuran-2 sulfonyl chloride (0.65 g, 3.0 mmol) and pyridine (3.0 ml) were added and the reaction was heated to 100 OC for 4 h, cooled to room temperature, poured onto a mixture of ice and 6M HCI (20 ml). The resulting suspension was filtered, rinsed with
H
2 0, and the cake was dissolved in EtOAc, washed with brine, dried over Na 2
SO
4 , 15 and concentrated to give 1.28 g brown solid. The solid was dissolved in MeOH/THF (40 ml/10 ml), treated with 4 M NaOH (4 ml) at 100 C for 15 min, and concentrated in vacuo. The residue was quenched with cold 1 M HCl, extracted with EtOAc (x2). The combined organic layer was washed with brine, dried over Na 2
SO
4 and concentrated. Re-crystallization from hot EtOH yielded 0.68 g (64%) of 20 Intermediate 6. 1 H-NMR (600 MHz, CDCI 3 ) 5 ppm 10.00 (s, 1 H), 8.13 (d, J=2.3 Hz, 1 H), 7.93 (d, J=9.1 Hz, 1 H), 7.64 - 7.68 (m, 1 H), 7.58 (dd, J=9.0, 2.5 Hz, 1 H), 7.45 - 7.53 (m, 3 H), 7.34 (ddd, J=7.9, 6.9, 1.0 Hz, 1 H). Intermediate 7 25 Benzofuran-2-sulfonic acid (2-amino-4-chloro-phenyl)-amide 0 O=S N H CI
NH
2 To a suspension of Intermediate 6 (217 mg, 0.61 mmol) in MeOH (25 ml) and saturated aqueous NH 4 CI (25 ml) was added zinc dust (1.0 g, 15.4 mmol). The 80 WO 2012/082633 PCT/US2011/064441 reaction was stirred at room temperature for 45 min. HOAc (1.0 ml) and zinc dust (1.0 g, 15.4 mmol) were added and the reaction was stirred for another 45 min and was filtered. The filtrate was extracted with EtOAc (x2). The combined organic layer was washed with brine, dried over Na 2
SO
4 , and concentrated. The crude product 5 was purified by flash column chromatography on silica gel (25% EtOAc-hexane) to yield 158 mg (79%) of Intermediate 7. 'H-NMR (600 MHz, CDCI 3 ) 5 ppm 7.65 (dt, J=7.4, 0.8 Hz, 1 H), 7.57 - 7.61 (m, 1 H), 7.50 (ddd, J=8.4, 7.1, 1.2 Hz, 1 H), 7.35 (ddd, J=8.0, 7.3, 0.9 Hz, 1 H), 7.30 (d, J=0.9 Hz, 1 H), 6.70 (d, J=2.3 Hz, 1 H), 6.59 (d, J=8.5 Hz, 1 H), 6.45 - 6.48 (m, 1 H), 10 6.32 (s, 1 H), 4.17 (br. s., 2 H). Intermediate 8 Thiophene-2-sulfonic acid (3-nitro-pyridin-2-yi)-amide
NO
2 N NH U=6 O S To a solution of 2-chloro-3-nitro-pyridine (CAS RN: 5470-18-8, 0.64 g, 4.0 15 mmol) in DMSO (4 ml) was added thiophene-2-sulfonic acid amide (CAS RN: 6339 87-3, 0.33 g, 2.0 mmol) and K 2
CO
3 (0.55 g, 4.0 mmol). The mixture was stirred at 60 OC for 24 h, diluted with EtOAc, extracted with 1 M HCl, brine, dried over Na 2
SO
4 , and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (25%-40% EtOAc in hexanes) to yield Intermediate 8 20 (0.50 g, 87%) as yellow powder. 'H NMR (CHLOROFORM-d) 5 ppm: 10.27 (br. s, 1H), 8.63 (dd, J = 4.5,1.6 Hz, 1 H), 8.53 (dd, J = 8.2, 1.8 Hz, 1 H), 8.00 (dd, J = 3.8, 1.5 Hz, 1 H), 7.67 (dd, J = 5.0, 1.5 Hz, 1 H), 7.13 - 7.19 (m, 1 H), 7.08 - 7.12 (m, 1 H). Intermediate 9 25 Thiophene-2-sulfonic acid (5-chloro-3-nitro-pyridin-2-yI)-amide CI NO 2 In N NH O S 81 WO 2012/082633 PCT/US2011/064441 To a solution of 2-bromo-5-chloro-3-nitro-pyridine (CAS RN: 75806-86-9, 360 mg, 1.5 mmol) in DMSO (2 ml) was added thiophene-2-sulfonic acid amide (CAS RN: 6339-87-3, 165 mg, 1.0 mmol) and K 2
CO
3 (276 mg, 2.0 mmol). The mixture was stirred at 60 C for 24 h, diluted with EtOAc, extracted with 1M HCl, brine, dried 5 over Na 2
SO
4 , and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (0%-100% EtOAc in hexanes) to yield Intermediate 9 (245 mg, 77%) as light brown solid. 'H NMR (METHANOL-d 4 ) 5: 8.57 - 8.63 (m, 2H), 7.95 (dd, J = 4.0, 1.3 Hz, 1 H), 7.86 (dd, J = 5.0, 1.5 Hz, 1H), 7.14 (dd, J = 5.1, 4.0 Hz, 1H). 10 Intermediate 10 Thiophene-2-sulfonic acid (3-amino-pyridin-2-yi)-amide
NH
2 N NH U=6 O/ , ox To a solution of Intermediate 8 (175 mg, 0.61 mmol) in MeOH (30 ml) and 1 M HCl (2 ml) was added Pd-C (10%, 65 mg, 0.061 mmol). The reaction was 15 pressurized under 45 psi H 2 for 3 h using Parr apparatus, filtered, and the filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (50%-100% EtOAc in hexanes, then 2:98 Et 3 N:EtOAc, then 2:20:80 Et 3 N:MeOH:CH 2
CI
2 ) to yield Intermediate 10 (157 mg, 84%) as off white solid. 20 1 H NMR (CHLOROFORM-d) 5: 7.61 (dd, J = 3.7, 1.3 Hz, 1 H), 7.44 (dd, J = 5.0, 1.2 Hz, 1 H), 6.96 - 7.03 (m, 2H), 6.83 (dd, J = 7.6, 1.5 Hz, 1 H), 6.56 (dd, J = 7.6, 6.2 Hz, 1H). Intermediate 11 Thiophene-2-sulfonic acid (3-amino-5-chloro-pyridin-2-yI)-amide CI
NH
2 N NH O~S 25 S 82 WO 2012/082633 PCT/US2011/064441 To a solution of Intermediate 9 (111 mg, 0.35 mmol) in MeOH (15 ml) was added aqueous NH 4 CI (15 ml) and zinc dust (0.56 g, 8.7 mmol). The mixture was stirred at room temperature for 2 h, filtered and extracted with EtOAc. The organic layer was washed with brine, dried over Na 2
SO
4 , and concentrated in vacuo. The 5 crude product was purified by flash column chromatography on silica gel (30% 100% EtOAc in hexanes, then 10% MeOH in CH 2 Cl 2 ) to yield Intermediate 11 (75 mg, 75%).C9H 8
CIN
3
O
2
S
2 (289.8). MS (ESI-): 288/290/ [M-H]-. Intermediate 12 N-(4,5-dichloro-2-(2-methylpropylsu Ifonamido)phenyl)-N-(ethoxymethyl) 10 thiophene-2-sulfonamide o=s S CI N O CI NH 0= 0 Sulfonamide formation: To a solution of Intermediate 2 (80 mg, 0.21 mmol) and DMAP (5.1 mg, 0.042 mmol, 0.2 eq.) in CHCl 3 (0.8 ml) and acetone (0.8 ml) was added isobutanesulfonyl chloride (32.9 pl, ca. 39 mg, 0.25 mmol, 1.2 eq.) at 15 room temp. followed by Et 3 N (87.2 pl, ca. 63 mg, 0.62 mmol, 3 eq.). The orange brown solution was stirred at 500C overnight. Water and EtOAc were added at room temp. and extraction with EtOAc followed. The organic layer was dried (Na 2
SO
4 ), filtered and concentrated. Chromatography on silica gel (hexane/CH 2
C
2 /Et 2 O 5:5:0.5 to 5:5:1) afforded the corresponding type Intermediate 12 product (43 mg, 20 41%) as light yellow oil. 1 H-NMR (CDCI 3 ): 5 ppm 7.85 (s, 1H); ca. 7.85-7.84 (partially hidden signal, 1H); 7.74 (dd, J = 1.3, 5.0, 1H); 7.54 (dd, J = 1.3, 3.8, 1H); 7.15 (dd, J = 3.8, 5.0, 1H); 7.00 (s, 1H); 5.05-4.88 (br. signal, 2H); 3.75-3.60 (br. signal, 2H); 3.04 (d, J = 6.6, 2H); 2.43-2.30 (heptet, 1H); 1.28 (t, J = 7.0, 3H); 1.14 (d, J = 6.7, 6H). 25 Preparation of Specific Compounds of the Invention: Compound 1 N-(4,5-dichloro-2-{[(3-chloro-4-fluorophenyl)sulfonyl]amino}phenyl) thiophene-2-sulfonamide 83 WO 2012/082633 PCT/US2011/064441 CI 1NH CI NH o LK CI F To Intermediate 3 (47 mg, 0.082 mmol) and EtOH (0.2 ml) was added 4M HCI/dioxane (1 ml) at room temp. The solution was stirred for 42 h at room temp. and then concentrated. Chromatography on silica gel (CH 2 Cl 2 / MeOH 9:1) afforded 5 Compound 1 (24.9 mg, 59%) as off-white solid.
C
16
H
10 Cl 3
FN
2 0 4
S
3 (515.81). HPLC-MS (acidic mobile phase, ESI-): tR = 2.14 min, 517/515/513 [M-H]-. 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.5-ca. 9 (br. signal, ca. 1H); 7.99-7.95 (m, 2H); 7.74-7.69 (m, 1H); 7.63 (d, J = 8.9, 1H); 7.58-7.55 (m, 1H); 7.30 (s, 1H); 7.17 (dd, J = 3.8, 5.0, 1H); 7.15 (s, 1H). 10 Compound 2 N-{4,5-dichloro-2-[(isobutylsulfonyl)amino]phenyl}thiophene-2-sulfonamide CI N H CI N H -I To Intermediate 12 (42 mg, 0.084 mmol) in EtOH (0.2 ml) was added 4M HCI/dioxane (2 ml) at room temp. The solution was stirred for 72 h at room temp. 15 and then concentrated. Chromatography on silica gel (CH 2 Cl 2 / MeOH 95:5 to 9:1) afforded Compound 2 (29.8 mg, 80%) as white solid.
C
14
H
16 Cl 2
N
2 0 4
S
3 (443.39). HPLC-MS (basic mobile phase, ESI-): tR = 1.66 min, 443/441 [M-H]-. 1 H-NMR (CDCI 3 ): 5 ppm 7.71 (dd, J = 1.3, 5.0, 1 H); 7.65 (s, 1 H); 7.55 (dd, J = 1.3, 3.8, 1H); 7.14 (dd, J = 3.8, 5.0, 1H); 7.05 (s, 1H); 6.97, 6.96 (2 20 partially separated s, 2x1H); 3.02 (d, J = 6.6, 2H); 2.42-2.28 (heptet, 1H); 1.14 (d, J = 6.6, 6H). Compound 3 N-(4,5-dichloro-2-{[(3,5-difluorophenyl)sulfonyl]amino}phenyl) thiophene-2-sulfonamide 84 WO 2012/082633 PCT/US2011/064441 CI 1 H CI N H O=S F F Preparation according to Method C (18% yield) from Intermediate 1.
C
1 6
H
10 Cl 2
F
2
N
2 0 4
S
3 (499.36). HPLC-MS (acidic mobile phase, ESI-): tR = 2.16 min, 499/497 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.4-ca. 9.3 (br. signal, ca. 2H); 8.00 (dd, J = 1.3, 5.0, 1 H); 7.68 (tt, J = 2.3, 9.2, 1 H); 7.59 (dd, J = 1.3, 3.8, 1 H); 7.54-7.43 (m, 2H); 7.31 (s, 1 H); 7.18 (dd, J = 3.8, 5.0, 1 H); 7.13 (s, 1 H). Compound 4 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,4-dimethyl 10 1,3-thiazole-5-sulfonamide o sr CI NH CI N H SAN o s Preparation according to Method A (10% yield) from Intermediate 1.
C
1 5
H
13 Cl 2
N
3 0 4
S
4 (498.45). HPLC-MS (acidic mobile phase, ESI-): tR = 1.98 min, 498/496 [M-H]-. 15 1 H-NMR (DMSO-d 6 ): 5 ppm 10.3-9.3 (br. signal, ca. 2H); 7.99 (dd, J = 1.3, 5.0, 1H); 7.60 (dd, J = 1.3, 3.8, 1H); 7.31, 7.27 (2s, 2x1H); 7.18 (dd, J = 3.8, 5.0, 1H); 2.62, 2.33 (2s, 2x3H). Compound 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,5-dimethylisoxazole-4 20 sulfonamide 85 WO 2012/082633 PCT/US2011/064441 0O=S S o CI1 0 C N 0 Preparation according to Method A (18% yield) from Intermediate 1.
C
1 5
H
13 Cl 2
N
3 0 5
S
3 (482.38). HPLC-MS (acidic mobile phase, ESI-): tR = 2.01 min, 482/480 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.3-ca. 9.5 (br. signal, ca. 2H); 8.00 (dd, J = 1.2, 4.9, 1H); 7.61 (dd, J = 1.3, 3.8, 1H); 7.31, 7.21 (2s, 2x1H); 7.19 (dd, J = 3.9, 5.0, 1H); 2.40, 2.19 (2s, 2x3H). Compound 6 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxoindoline-5 10 sulfonamide o=s s NH CI NH U=s NH 0 Preparation according to Method A (24% yield) from Intermediate 1.
C
1 8
H
13 Cl 2
N
3 0 5
S
3 (518.41). HPLC-MS (acidic mobile phase, ESI-): tR = 1.88 min, 518/516 [M-H]-. 15 1 H-NMR (DMSO-d 6 ): 5 ppm 10.84 (s, 1H); ca. 10.1-ca. 10.65 (br. signal, ca. 1H); ca. 10.65-ca. 9.3 (br. signal, ca. 1 H); 7.99 (signal appears as d, "J" = 4.9, 1 H); 7.60 7.55 (m, 3H); 7.28, 7.19 (2s, 2x1H); 7.17 (dd, J = 3.8, 4.9, 1H); 6.93 (d, J = 8.7, 1H); 3.55 (s, 2H). Compound 7 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3-dihydro-1,3 benzoxazole-6-sulfonamide 86 WO 2012/082633 PCT/US2011/064441 o I CI N H C )cNH U=s NH 0 Preparation according to Method A (31 % yield) from Intermediate 1.
C
17
H
11 Cl 2
N
3 0 6
S
3 (520.39). HPLC-MS (basic mobile phase, ESI-): tR = 1.21 min, 520/518 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 12.4-ca. 11.95 (br. signal, 1H); ca. 10.1-ca. 9.3 (br. signal, 2H); 7.98 (dd, J = 1.3, 5.0, 1 H); 7.65 (d, J = 1.6, 1 H); 7.56-7.52 (m, 2H); 7.31 (s, 1H); 7.23 (d, J = 8.3, 1H); 7.16 (dd, J = 3.7, 4.9, 1H); 7.15 (s, 1H). Compound 8 4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic 10 acid o =s CI 1 H CI NH 0=6 GOOH Preparation according to Method A (26% yield) from Intermediate 1.
C
17
H
12 Cl 2
N
2 0 6
S
3 (507.39). HPLC-MS (acidic mobile phase, ESI-): tR = 1.78 min, 507/505 [M-H]-. 15 1 H-NMR (DMSO-d 6 ): 5 ppm 10.3-10.05 (br. signal, 1H); 9.58 (s, 1H); 8.06 (s, 1H); 7.88 (partially resolved dd, J = 0.9, 5.0, 1 H); 7.75 (s, 4H); 7.46-7.45 (m, 2H); 7.06 7.03 (t-like signal, 1 H). Compound 9 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 20 methoxybenzoic acid 87 WO 2012/082633 PCT/US2011/064441 O= O o s CI NH CII O, y COOH OMe Preparation according to Method B (31 % yield) from Intermediate 1.
C
1 8
H
14 Cl 2
N
2 0 7
S
3 (537.41). HPLC-MS (basic mobile phase, ESI-): tR = 1.16 min, 537/535 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm 10.80 (s, 1H); 10.4-10.15 (br. signal, 1H); 8.73 (s, 1H); 8.30 (d, J = 2.3, 1 H); 8.05 (dd, J = 1.4, 5.0, 1 H); 7.81 (dd, J = 2.3, 8.6, 1 H); 7.55 (dd, J = 1.4, 3.8, 1H); 7.26-7.21 (m, 2H); 6.71 (s, 1H); 4.14 (s, 3H). Compound 10 N-(4,5-dichloro-2-{[(2,4-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 10 sulfonamide o 0= S CI1 CI NH OMe 0=s 0 HOMe Preparation according to Method A (40% yield) from Intermediate 1.
C
1 8
H
16 Cl 2
N
2 0 6
S
3 (523.43). HPLC-MS (basic mobile phase, ESI-): tR = 1.58 min, 523/521 [M-H]-. 15 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.1-ca. 9.7 (br. signal, ca. 1H); 9.16 (br. s, 1H); 7.99 (signal appears as partially resolved d, "J" = 4.2, 1 H); 7.62 (d, J = 8.8, 1 H); 7.54 (signal appears as partially resolved d, "J" = 2.5, 1H); 7.39 (s, 1H); 7.17 (t-like signal, "J" = 4.3, 1 H); 7.04 (s, 1 H); 6.73 (d, J = 2.3, 1 H); 6.61 (dd, J = 2.3, 8.8, 1 H); 3.91, 3.83 (2s, 2x3H). 20 Compound 11 N-[4,5-dichloro-2-({[2 (methylsulfonyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide 88 WO 2012/082633 PCT/US2011/064441 o n/ CI NH SO 2 Me 0 =S6N Preparation: DIPEA (3 eq.), CH 2 Cl 2 , rt (76% yield) from Intermediate 1.
C
17
H
14 Cl 2
N
2 0 6
S
4 (541.47). HPLC-MS (acidic mobile phase, ESI-): tR = 1.99 min, 541/539 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.1-ca. 9 (2 br. signals, ca. 2H); 8.27 (partially resolved dd, J = 1.2, 7.9, 1 H); 8.02-7.94 (m, 3H); 7.89-7.84 (m, 1 H); 7.63 (s, 1 H); 7.44 (dd, J = 1.4, 3.8, 1H); 7.16 (dd, J = 3.8, 5.0, 1H); 6.68 (br. s, 1H); 3.51 (s, 3H). Compound 12 Methyl 4-[({4,5-dichloro 10 [(2thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoate 0 CI NH CI aNH COOMe Preparation according to Method A (33% yield) from Intermediate 1.
C
1 8
H
14 Cl 2
N
2 0 6
S
3 (521.42). HPLC-MS (basic mobile phase, ESI-): tR = 1.58 min, 521/519 [M-H]-. 15 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.2-ca. 9.5 (br. signal, ca. 2H); 8.12 (d, J = 8.6, 2H); 7.98 (dd, J = 1.3, 5.0, 1 H); 7.87 (d, J = 8.7, 2H); 7.55 (dd, J = 1.4, 3.8, 1 H); 7.24, 7.20 (2s, 2x1H); 7.16 (dd, J = 3.8, 5.0, 1H); 3.90 (s, 3H). Compound 13 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2H-chromene-6 20 sulfonamide 89 WO 2012/082633 PCT/US2011/064441 o NH CI 1 CI N H 0O Preparation according to Method A (51 % yield) from Intermediate 1.
C
19
H
12 Cl 2
N
2 0 6
S
3 (531.41). HPLC-MS (acidic mobile phase, ESI-): tR = 2.04 min, 531/529 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm 10.1-9.5 (br. signal, 2H); 8.21 (d, J = 2.3, 1H); 8.18 (d, J = 9.7, 1 H); 7.98 (dd, J = 1.3, 5.0, 1 H); 7.89 (dd, J = 2.3, 8.8, 1 H); 7.59-7.55 (m, 2H); 7.33 (s, 1H); 7.16 (dd, J = 3.8, 5.0, 1H); 7.15 (s, 1H); 6.64 (d, J = 9.6, 1H). Compound 14 6-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}imidazo[2,1 10 b][1,3]thiazole-5-sulfonamide O=:S S CI NH CI N CI Preparation according to Method C (8% yield) from Intermediate 1.
C
1 5
H
9
CI
3
N
4 0 4
S
4 (543.88). HPLC-MS (acidic mobile phase, ESI-): tR = 1.99 min, 545/543/ 541 [M-H]-. 15 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.4-ca. 9.3 (br. signal, ca. 1H); 7.98 (dd, J = 1.2, 5.0, 1 H); 7.91, 7.63 (2d, J = 4.5, 2x1 H); 7.56 (dd, J = 1.3, 3.8, 1 H); 7.31 (s, 1 H); 7.16 (dd, J = 3.9, 4.9, 1H); 7.12 (s, 1H). Compound 15 N-{4,5-d ich loro-2-[(2-th ienylsu Ifonyl)amino]phenyl}-2,5-d imethylfuran-3 20 sulfonamide 90 WO 2012/082633 PCT/US2011/064441 O=s S CI 1NH CI NH O S 0 DO Preparation according to Method A (40% yield) from Intermediate 1.
C
1 6
H
14 Cl 2
N
2 0 5
S
3 (481.39). HPLC-MS (acidic mobile phase, ESI-): tR = 2.15 min, 481/479 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.1-ca. 9.7 (br. signal, ca. 1H); ca. 9.7-ca. 9.4 (br. signal, 1 H); 8.01 (dd, J = 1.4, 5.0, 1 H); 7.59 (dd, J = 1.4, 3.8, 1 H); 7.30, 7.28 (2s, 2x1H); 7.18 (dd, J = 3.8, 5.0, 1H); 6.15 (signal appears as partially resolved d, "J" = 1.0, 1 H); 2.28, 2.21 (2s, 2x3H). Compound 16 10 N-[4,5-dichloro-2-({[4-(3,5-dimethyl-1H-pyrazol-1 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide CI 3NH N'N Preparation according to Method A (51 % yield) from Intermediate 1. C21H 18 Cl 2
N
4 0 4
S
3 (557.49). 15 HPLC-MS (basic mobile phase, ESI-): tR = 1.61 min, 557/555 [M-H]-. 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10-ca. 9.5 (br. signal, 2H); 7.97 (dd, J = 1.3, 5.0, 1 H); 7.81, 7.75 (2d, J = 9.0, 2x2H); 7.56 (dd, J = 1.3, 3.8, 1 H); 7.27, 7.22 (2s, 2x1H); 7.16 (dd, J = 3.8, 5.0, 1H); 6.15 (s, 1H); 2.38, 2.19 (2s, 2x3H). Compound 17 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-pyrazole-3 sulfonamide 91 WO 2012/082633 PCT/US2011/064441 o=s S CI NH CI NH O=s N-N Preparation according to Method A (57% yield) from Intermediate 1.
C
1 4
H
12 Cl 2
N
4 0 4
S
3 (467.37). HPLC-MS (basic mobile phase, ESI-): tR = 1.41 min, 467/465 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm 10-9.6 (br. signal, 2H); 7.99 (dd, J = 1.3, 5.0, 1H); 7.91 (d, J = 2.3, 1H); 7.60 (dd, J = 1.3, 3.8, 1H); 7.47, 7.32 (2s, 2x1H); 7.17 (dd, J = 3.8, 5.0, 1 H); 6.64 (d, J = 2.3, 1 H); 3.93 (s, 3H). Compound 18 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-1H-indole-4 10 sulfonamide o 0 H CI NH CI N H o N s.. Preparation according to Method A, 15 min (45% yield) from Intermediate 1.
C
19
H
15 Cl 2
N
3 0 4
S
3 (516.44). HPLC-MS (acidic mobile phase, ESI-): tR = 2.04 min, 516/514 [M-H]-. 15 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10-ca. 9.5 (br. signal, ca. 2H); 7.96 (dd, J = 1.2, 5.0, 1 H); 7.82 (d, J = 7.8, 1 H); 7.59 (d, J = 3.1, 1 H); 7.52 (partially resolved dd, J = 0.8, 7.5, 1 H); 7.49 (partially resolved dd, J = 1.2, 3.9, 1 H); 7.30 (t, J = 7.3, 1 H); 7.21 (s, 1H); 7.14 (dd, J = 3.8, 5.0, 1H); 7.10 (s, 1H); 6.74 (partially resolved dd, J = 0.7, 3.1, 1 H); 3.86 (s, 3H). 20 Compound 19 N-(4,5-dichloro-2-{[(2,5-dimethyl-3-th ienyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 92 WO 2012/082633 PCT/US2011/064441 o # o =- s CI N H CI N H o=s S Preparation according to Method A (44% yield) from Intermediate 1.
C
1 6
H
14 Cl 2
N
2 0 4
S
4 (497.46). HPLC-MS (acidic mobile phase, ESI-): tR = 2.20 min, 497/495 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.2-ca. 9.3 (2 br. signals, ca. 2H); 8.00 (signal appears as partially resolved d, "J" = 4.0, 1 H); 7.60 (signal appears as partially resolved d, "J" = 2.7, 1H); 7.28 (s, 1H); 7.18 (partially hidden dd, J = 3.8, 5.0, 1H); ca. 7.16 (s, 1H); 6.84 (signal appears as partially resolved d, "J" = 1.1, 1H); 2.38, 2.35 (2s, 2x3H). 10 Compound 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide o 0 S S CI 1NH CI NH O=S 'I N Preparation according to Method A (33% yield) from Intermediate 1.
C
1 5
H
11 Cl 2
N
3 0 4
S
3 (464.37). 15 HPLC-MS (acidic mobile phase, ESI-): tR = 1.94 min, 464/462 [M-H]-. 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.4-ca. 9.2 (br. signal, ca. 1H); 8.88 (d, J = 1.8, 1H); 8.84 (dd, J = 1.5, 4.8, 1H); 8.11 (ddd, J = 1.7, 2.5, 8.1, 1H); 7.98 (dd, J = 1.3, 5.0, 1H); 7.62 (dd, J = 4.5, 7.8, 1H); 7.54 (dd, J = 1.4, 3.8, 1H); 7.29 (s, 1H); 7.17 (s, 1H); 7.167 (partially hidden dd, J = 3.8, 5.0, 1H). 20 Compound 21 N-{(4,5-dichloro-2-[(3,5-dichloro-4-hydroxyphenyl)sulfonyl] amino}phenyl)thiophene-2-sulfonamide 93 WO 2012/082633 PCT/US2011/064441 o=s S CI N H CI NH 0=, CI I, H CI Preparation according to Method A (19% yield) from Intermediate 1.
C
1 6
H
10 Cl 4
N
2 0 5
S
3 (548.27). HPLC-MS (basic mobile phase, ESI-): tR = 1.21 min, 549/547/545 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10.8-ca. 9.1 (br. signal, ca. 2H); 7.99 (dd, J = 1.3, 5.0, 1H); 7.69 (s, 2H); 7.56 (dd, J = 1.4, 3.8, 1H); 7.30 (s, 1H); 7.17 (dd, J = 3.9, 5.0, 1H); 7.15 (s, 1H). Compound 22 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,2-dimethyl-1 H-imidazole 10 4-sulfonamide os 0=S S CI 1H O0S N Preparation according to Method C (32% yield) from Intermediate 1.
C
1 5
H
14 Cl 2
N
4 0 4
S
3 (481.40). HPLC-MS (basic mobile phase, ESI-): tR = 1.44 min, 481/479 [M-H]-. 15 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 11-ca. 10 (br. signal, ca. 1H); 9.8-9.5 (br. signal, 1 H); 7.98 (signal appears as d, "J" = 5.0, 1 H); 7.81 (s, 1 H); 7.61 (signal appears as d, "J" = 3.7, 1H); 7.53, 7.41 (2s, 2x1H); 7.16 (signal appears as t, "J" = 4.4, 1H); 3.60, 2.36 (2s, 2x3H). Compound 23 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-methylquinoline-8 sulfonamide 94 WO 2012/082633 PCT/US2011/064441 o CI N H CI l.NH N I S o | Preparation according to Method A (30% yield) from Intermediate 1.
C
20
H
15 Cl 2
N
3 0 4
S
3 (528.45). HPLC-MS (acidic mobile phase, ESI-): tR = 2.14 min, 528/526 [M-H]-. 5 1 H-NMR (DMSO-d 6 ): 5 ppm ca. 10-ca. 9.6 (br. signal, 2H); 9.04 (partially resolved d, J = 1.7, 1 H); 8.37 (signal appears as s, 1 H); 8.25 (signal appears as t, J = 8.5, 2H); 7.95 (signal appears as partially resolved d, "J" = 5.2, 1 H); 7.73-7.68 (t-like signal, "J" = 7.7, 1 H); 7.58 (s, 1 H); 7.43 (unresolved "d", "J" = 2.5, 1H); 7.14-7.11 (partially resolved t-like signal, "J" = 4.3, 1 H); 6.79 (s, 1 H); 2.57 (s, 3H). 10 Compound 24 N-{5-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide o S O=S NH Cj" 02 CI N' H To a solution of N-(2-amino-4-chlorophenyl)thiophene-2-sulfonamide (CAS RN: 926205-90-5) (140 mg, -0.47 mmol) in pyridine (2.5 ml) was added 15 benzofuran-2-sulfonyl chloride (102 mg, 0.47 mmol) and the mixture was stirred at room temperature for 16 h. More benzofuran-2-sulfonyl chloride (51 mg, 0.24 mmol) was added and the reaction was stirred for another 24 h, concentrated in vacuo to remove most of solvent. The residual thick syrup was quenched with 6M HCl and diluted with H 2 0. The resulting suspension was filtered and washed with H 2 0 (x3). 20 The crude product was purified by flash column chromatography on silica gel (25 50% EtOAc-hexane) to yield 43 mg of product slightly contaminated with impurities. This material was triturated with CH 2
CI
2 to form a sandy colored solid, which was filtered and rinsed with minimal amount of CH 2
CI
2 to yield 23 mg (10%) of Compound 24. 95 WO 2012/082633 PCT/US2011/064441 1 H-NMR (600 MHz, CD 3 OD) 5 ppm 7.73 (dd, J=5.0, 1.5 Hz, 1 H), 7.70 - 7.72 (m, 1 H), 7.60 - 7.63 (m, 1 H), 7.51 (ddd, J=8.5, 7.2, 1.3 Hz, 1 H), 7.41 (dd, J=3.8, 1.2 Hz, 1 H), 7.37 (dd, J=1.9, 0.7 Hz, 1 H), 7.34 - 7.36 (m, 1 H), 7.29 (d, J=2.3 Hz, 1 H), 7.07 (dd, J=8.8, 2.3 Hz, 1 H), 7.05 (dd, J=5.0, 3.8 Hz, 1 H), 6.95 (d, J=8.5 Hz, 1 H), 5 4.57 (br. s., 2 H). Compound 25 N-{4-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide 0 O=S NH Cj" 02 CI N' H To a solution of Intermediate 7 (158 mg, 0.49 mmol) in pyridine (3.0 ml) was 10 added thiophene-2-sulfonyl chloride (90 mg, 0.49 mmol) and the mixture was stirred at room temperature for 16 h. The solvent was removed in vacuo and the residue was purified by flash column chromatography on silica gel (25-50% EtOAc-hexane) to yield 64 mg of the desired product slightly contaminated with impurities. Further purification with preparative TLC (50% EtOAc-hexane) yielded 52 mg (23%) of 15 Compound 25. 1 H-NMR (600 MHz, CD 3 OD) 5 ppm 7.76 (dd, J=5.0, 1.2 Hz, 1 H), 7.69 (dd, J=7.9, 1.2 Hz, 1 H), 7.62 (dd, J=8.5, 0.6 Hz, 1 H), 7.51 (ddd, J=8.4, 7.3, 1.3 Hz, 1 H), 7.46 (dd, J=3.8, 1.5 Hz, 1 H), 7.32 - 7.37 (m, 2 H), 7.13 - 7.16 (m, 1 H), 7.06 - 7.11 (m, 3 H). 20 Compound 26 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,2 dimethylchromane-6-sulfonamide 0 C1I CI NH 0 NH / = 0 Preparation: Method A (63% yield) from Intermediate 5. 25 C 25
H
23
CIN
2 0 6
S
2 (547.04). 96 WO 2012/082633 PCT/US2011/064441 HPLC-MS (basic mobile phase, ESI-): tR = 1.55 min, 547/545 [M-H]-. 'H-NMR (DMSO-d 6 ): 5 ppm 10.5-9.8 (br. signal, ca. 1H); 9.28 (s, 1H); 7.79 (partially resolved dd, J = 0.4, 7.6, 1 H); 7.72 (dd, J = 0.8, 8.4, 1 H); 7.66 (s, 1 H); 7.56 (m, 1 H); 7.50 (d, J= 2.3, 1H); 7.41 (m, 1H); 7.32 (dd, J = 2.4, 8.7, 1H); 7.20-7.10 (m, 2H); 5 7.08 (partially resolved dd, J = 0.4, 8.7, 1H); 6.75 (d, J = 8.7, 1H); 2.74 (t, J = 6.6, 2H); 1.76 (t, J = 6.6, 2H); 1.27 (s, 6H). Compound 27 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-methyl-1,3 benzothiazole-6-sulfonamide s 0 NH CI NH -6 1~S 10 0 Preparation: Method A (60 % yield) from Intermediate 5.
C
22
H
16
CIN
3 0 5
S
3 (534.03). HPLC-MS (basic mobile phase, ESI-): tR = 1.36 min, 532/534 [M-H]-. 1 H-NMR (DMSO-d 6 ): 5 ppm 10.4-9.8 (br. signal, ca. 1H); 9.8-9.6 (broad signal, ca. 15 1 H); 9.59 (s, 1 H); 8.50 (d, J = 1.6, 1 H); 7.98 (d, J = 8.6, 1 H); 7.80-7.70 (m, 3H); 7.62 (s, 1H); 7.56 (m, 1H); 7.40 (m, 1H); 7.14-7.10 (m, 2H); 7.00 (dd, partially resolved, J = 1.3, 8.5, 1H); 2.84 (s, 3H). Compound 28 N-[5-chloro-2-({[3-(2-methylpyrimidin-4-yl)phenyl]sulfonyl}amino)phenyl]-1 20 benzofuran-2-sulfonamide 0 C1 NH 0 NH / 0 N -- N Preparation: Method A (20 % yield) from Intermediate 5.
C
25
H
19
CIN
4 0 5
S
2 (555.03). 97 WO 2012/082633 PCT/US2011/064441 HPLC-MS (acidic mobile phase, ESI*): tR = 2.11 min, 555/557 [M+H]*. 1H-NMR (DMSO-d 6 ): 5 ppm 10.6-9.8 (br. signal, ca. 1H); 9.8-9.5 (br. signal, ca. 1H); 8.81 (d, J = 5.3, 1 H); 8.56 (t, J = 1.6, 1 H); 8.40 (d, J = 7.9, 1 H); 7.89 (d, J = 5.3, 1 H); 7.82 (m, 1 H); 7.76 (d, J = 7.6, 1 H); 7.68 (m, 2H); 7.62 (s, 1 H); 7.54 (m, 1 H); 7.39 (m, 5 1H); 7.18-7.14 (m, 2H); 7.06 (d, J = 9.1, 1H); 2.70 (s, 3H). Compound 29 N-{5-chloro-2-[(isobutylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide 0 clI CI NH 0 NH o=s 0 Preparation: Method A (11% yield) from Intermediate 5. 10 C 1 8
H
19
CIN
2 0 5
S
2 (442.94). HPLC-MS (basic mobile phase, ESI-): tR = 1.86 min, 441/443 [M-H]-. 1H-NMR (DMSO-d 6 ): 5 ppm 10.8-9.8 (br. signal, ca. 1H); 8.91 (s, 1H); 7.78 (d, J = 7.7, 1H); 7.72 (d, J = 8.4, 1H); 7.66 (s, 1H); 7.56 (m, 1H); 7.44-7.36 (m, 2H); 7.27 (d, J = 8.9, 1 H); 7.23 (d, J = 2.4, 1 H); 2.84 (d, J = 6.5, 2H); 2.04 (septuplet, J = 6.7, 15 1 H); 0.91 (d, J = 6.7, 6H). Compound 30 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}isoquinoline-5 sulfonamide 0 C1I C I N H 0 NH O=$/ 0 N 20 Preparation: Method A (51% yield) from Intermediate 5.
C
23
H
16
CIN
3 0 5
S
2 (513.97). HPLC-MS (acidic mobile phase, ESI*): tR= 1.86 min, 514/516 [M+H]*. 98 WO 2012/082633 PCT/US2011/064441 'H-NMR (DMSO-d 6 ): 5 ppm 10.4-9.6 (br. signal, ca. 2H); 9.47 (d, J = 0.7, 1H); 8.65 (d, J = 6.2, 1H); 8.45 (d, J = 8.2, 1H); 8.37 (d, J = 6.1, 1H); 8.25 (dd, J = 1.2, 7.4, 1 H); 7.76 (m, 2H); 7.69 (dd, J = 0.7, 8.4, 1 H); 7.59 (s, 1 H); 7.54 (m, 1 H); 7.39 (m, 1 H); 7.08-7.03 (m, 2H); 6.87 (d, J = 8.7, 1 H). 5 Compound 31 N-(5-ch loro-2-{[(2,4-d imethoxyphenyl)su lfonyl]am ino}phenyl)-1 -benzofuran-2 sulfonamide 0 N clI CI NH NH 0 0 Preparation: Method A (54 % yield) from Intermediate 5. 10 C 22
H
19
CIN
2 0 7
S
2 (522.98). MS (ESI*): 523 [M+H]*. 1 H-NMR (DMSO-d 6 ): 5 ppm 10.6-9.8 (br. signal, ca. 1H); 9.02 (s, 1H); 7.78 (d, J = 7.6, 1H); 7.71 (d, J = 8.4, 1H); 7.65 (s, 1H); 7.55 (m, 2H); 7.40 (t, J = 7.5, 1H); 7.15 (s, 2H); 7.01 (t partially resolved, J = 1.2, 1 H); 6.71 (d, J = 2.2, 1 H); 6.56 (dd, J = 15 2.3, 8.8, 1 H); 3.91 (s, 3H); 3.81 (s, 3H). Compound 32 ethyl 5-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]-3-furoate o / 11 0 00 20 Preparation: Method C (16 % yield) from Intermediate 5. C21 H 17
CIN
2 0 8
S
2 (524.95). HPLC-MS (acidic mobile phase, ESI-): tR = 2.30 min, 523/525 [M-H]-. 99 WO 2012/082633 PCT/US2011/064441 'H-NMR (DMSO-d 6 ): 5 ppm 10.9-9.5 (br. signal, ca. 2H); 8.61 (d, J = 0.9, 1H); 7.79 (d, J = 7.4, 1 H); 1.71 (dd, J = 0.7, 8.4, 1 H); 7.67 (s, 1 H); 7.55 (m, 1 H); 7.40 (m, 1 H); 7.26-7.21 (m, 2H); 7.19 (d, J = 2.2, 1H); 7.13 (d, J = 8.6, 1H); 4.25 (quartet, J = 7.1, 2H); 1.27 (t, J = 7.1, 3H). 5 Compound 33 N-(5-chloro-2-{[(2,5-dichloro-3-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide 0 11 0I SH C11 Icl NH o c Preparation: Method C (30 % yield) from Intermediate 5. 10 C 1 8
H
11
C
3
N
2 0 5
S
3 (537.84). HPLC-MS (basic mobile phase, ESI-): tR = 1.70 min, 535/537 [M-H]-. 1 H-NMR (DMSO-d 6 ): 5 ppm 10.6-9.4 (br. signal, ca. 2H); 7.80 (dd, J = 0.7, 7.8, 1H); 7.73-7.69 (m, 2H); 7.55 (m, 1 H); 7.40 (m, 1 H); 7.33-7.20 (m, 3H); 7.09 (d, J = 8.7, 1 H). 15 Compound 34 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5,6-dichloropyridine 3-sulfonamide 0 S O=S C1 0 CI Preparation: Method C (28 % yield) from Intermediate 5. 20 C 19
H
12 Cl 3
N
3 0 5
S
2 (532.80). HPLC-MS (acidic mobile phase, ESI*): tR = 2.36 min, 532/534 [M+H]*. 1 H-NMR (DMSO-d 6 ): 5 ppm 10.7-9.5 (br. signal, ca. 2H); 8.60 (d, J = 2.2, 1H); 8.37 (d, J = 2.2, 1H); 7.80 (d, J = 7.4, 1H); 7.72 (dd, J = 0.7, 8.4, 1H); 7.67 (s, 1H); 7.56 (m, 1 H); 7.40 (m, 1 H); 7.22 (m, 2H); 7.04 (dd partially resolved, J = 0.5, 2.3, 1 H). 100 WO 2012/082633 PCT/US2011/064441 Compound 35 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methoxybenzoic acid 0 IC Cl NH 0 NH 0 0 HO 5 Preparation: Method B (17 % yield) from Intermediate 5.
C
22
H
17
CIN
2 0 8
S
2 (536.96). HPLC-MS (acidic mobile phase, ESI): tR = 1.68 min, 537/539 [M+H]*. 1 H-NMR (DMSO-d 6 ): 5 ppm 11.0-10.7 (br. signal, ca. 1H); 10.67 (s, 1H); 8.42 (d, J = 8.9, 1 H); 8.29 (d, J = 2.3, 1 H); 7.78 (m, 2H); 7.66-7.62 (m, 2H); 1.53 (m, 1 H); 7.44 10 7.36 (m, 2H); 7.23 (d, J = 8.7, 1H); 6.77 (d, J = 2.5, 1H); 4.14 (s, 3H). Compound 36 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 ethoxybenzoic acid 0 C1 NH 0 OH "'NH 0=S /0 0 15 Preparation: Method B (27% yield) from Intermediate 5.
C
23
H
19
CIN
2 0 8
S
2 (550.99). HPLC-MS (acidic mobile phase, ESI): tR = 1.77 min, 551/553 [M+H]*. 1 H-NMR (DMSO-d 6 ): 5 ppm 10.9-10.6 (br. signal, ca. 1H); 10.48 (s, 1H); 8.31 (d, J = 8.9, 1H); 8.25 (d, J = 2.3, 1H); 7.79-7.75 (m, 2H); 7.66-7.59 (m, 2H); 7.53 (m, 1H); 20 7.43-7.36 (m, 2H); 7.22 (d, J = 8.7, 1 H); 6.78 (d, J = 2.5, 1 H); 4.44 (quartet, J = 7.0, 2H); 1.47 (t, J = 6.9, 3H). 101 WO 2012/082633 PCT/US2011/064441 Compound 37 N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2 yl]thiophene-2-sulfonamide O=S N NH S
CF
3 O=S CI 0 5 To a solution Intermediate 10 (72 mg, 0.28 mmol) in pyridine (2 ml) was added 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (49 tl, 0.28 mmol) and the reaction was stirred at room temperature for 3 days, concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (50%-75% EtOAc in hexanes) to yield Compound 37 (26 mg, 18%). 10 1 H NMR (acetone-d6) 5 ppm: 8.27 (d, J = 2.1 Hz, 1H), 8.14 (dd, J = 8.4, 2.2 Hz, 1 H), 7.97 (dd, J = 7.6, 1.5 Hz, 1 H), 7.83 (dd, J = 6.4, 1.5 Hz, 1 H), 7.78 (d, J = 8.2 Hz, 1 H), 7.71 (dd, J = 5.0, 1.5 Hz, 1 H), 7.51 (dd, J = 3.7, 1.3 Hz, 1 H), 7.05 (dd, J = 5.0, 3.5 Hz, 1 H), 6.88 (dd, J = 7.8, 6.3 Hz, 1 H). Compound 38 15 N-[5-chloro-3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2 yl]thiophene-2-sulfonamide 0 11 N NH S CF3 C1 N CI NH _F O=S CI 0 To a solution of Intermediate 11 (75 mg, 0.26 mmol) in pyridine (2 ml) was added 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride (143 mg, 0.52 mmol) and 20 the reaction was stirred at 100 OC for 6 h, concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (50%-100% EtOAc in hexanes), followed by PTLC (EtOAc) to yield Compound 38 (24 mg, 17%). 1 H NMR (acetone-d6) 5 ppm: 8.52 (d, J = 8.5 Hz, 1H), 8.47 (s, 1H), 7.88 - 8.01 (m, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.58 (d, J = 4.7 Hz, 1H), 7.42 - 7.51 (m, 1H), 7.17 25 7.28 (m, 1 H), 6.91 - 7.01 (m, 1 H). 102 WO 2012/082633 PCT/US2011/064441 The synthetic methods used in the preparation of the other compounds of the invention is summarized in Table 1.Compounds 39 through 261 where prepared starting from Intermedite 1. Compound 262 was prepared from Intermedite 7. Compound 263 through 484 were prepared starting from Intermedite 5. 5 Table 1 Comp. Structure IUPAC compound name Synthesis No. 39 S N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method C C1 yl}furan-2-sulfonamide C H 40 N-{2-[(biphenyl-4 CI N CI NH ylsulfonyl)amino]-4,5 s dichlorophenyl}thiophene- Method A CI N 2-sulfonamide 41 S S N-(4,5-dichloro-2-{[(3,5 CI NH difluorophenyl)sulfonyl]ami Method C 0- 0S F no}phenyl)thiophene-2 CI N sulfonamide H F 42 S N-(4,5-dichloro-2-{[(3,5 CI NH dichlorophenyl)sulfonyl]am Method C IO inolphenyl)thiophene-2 CI N/ N sulfonamide ____ ____ NI_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ H 103 WO 2012/082633 PCT/US2011/064441 43 ;s , , '0N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A | 0 a yl}-3,5-dimethylisoxazole N 4-sulfonamide CI N 0' 44 S N-(4,5-dichloro-2-{[(4 chloro-2,5 CI NH difluorophenyl)sulfonyl]ami Method C 0%,0 no}phenyl)thiophene-2 NS F sulfonamide H F CI 45 CI NH N-[4,5-dichloro-2-({[4-(2 methylphenoxy)phenyl]sulf Method A CI N' onyl}amino)phenyl]thiophe H ne-2-sulfonamide 0 46 0, ,o N-{4,5-dichloro-2-[(2 CI N hthienylsulfonyl)amino]phen Method C I~a N yl}-5-isoxazol-3 ci s ylthiophene-2-sulfonamide H __/ 47 S N-(4,5-dichloro-2-{[(2,4 dimethylphenyl)sulfonyl]a Method A ci NH mino}phenyl)thiophene-2 sulfonamide CI N H 104 WO 2012/082633 PCT/US2011/064441 48 s 0 N-(4,5-dichloro-2-{[(2,6 C dichlorophenyl)sulfonyl]am M A CI a NH Method A 0 0 ci ino}phenyl)thiophene-2 1 sulfonamide 49 0 s 11 o:=sG CI NH N-(4,5-dichloro-2-{[(3 CI NH fluorophenyl)sulfonyl]amin Method A o}phenyl)thiophene-2 0=S=0 sulfonamide F 50 0 s II O=s CI NH CI NH N-[4,5-dichloro-2-({[4 (methylsulfonyl)phenyl]sulf Method A onyl}amino)phenyl]thiophe ne-2-sulfonamide o=s=o
CH
3 51 0 s II o:=s G CI NH a NH N-(4,5-dichloro-2-{[(3,4 CI NH difluorophenyl)sulfonyl]ami o=s=0 no}phenyl)thiophene-2 sulfonamide F F 105 WO 2012/082633 PCT/US2011/064441 52 0 s O=S CI N H N-(4,5-dichloro-2-{[(3 CI NH methylphenyl)sulfonyl]ami Method A I no}phenyl)thiophene-2 0=S=0 sulfonamide CH3 53 0 s O=S CI NH 5-chloro-N-{4,5-dichloro-2 CI NH [(2 1 thienylsulfonyl)amino]phen Method C yl}-3-methyl-1 S N CH 3 benzothiophene-2 sulfonamide CI 54 0 s o=s CI NH N-(4,5-dichloro-2-{[(4 CI NH chloro-3 I methylphenyl)sulfonyl]ami Method A 0S=s0 no}phenyl)thiophene-2 sulfonamide
CH
3 CI 106 WO 2012/082633 PCT/US2011/064441 55 0 s 11 CI N H a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-2-oxo-2,3-dihydro-1,3- Method A benzoxazole-6 sulfonamide 0 0 NH 56 o s CI NH CI a NH 4-[({4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen 0=s=0 yl}amino)sulfonyl]benzoic Method A acid O OH 57 0 s o=S CI NH CI NH 5-[({4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method B 030u yl}amino)sulfonyl]-2 methoxybenzoic acid OH .0 0
CH
3 107 WO 2012/082633 PCT/US2011/064441 58 o s O=s CI N H N-(4,5-dichloro-2-{[(3 CI NH chloro-4 I methylphenyl)sulfonyl]ami Method A o=s=o no}phenyl)thiophene-2 sulfonamide CI
CH
3 59 0 s I I O=s CI NH N-(4,5-dichloro-2-{[(3 CI NH cyanophenyl)sulfonyl]amin Method C _ _o}phenyl)thiophene-2 sulfonamide 60 0 s O=S CI NH a NH N-(4,5-dichloro-2-{[(4 CI NH methylphenyl)sulfonyl]ami o=s=o no}phenyl)thiophene-2 sulfonamide
CH
3 108 WO 2012/082633 PCT/US2011/064441 61 o S o=s-G CI N H N-(2-{[(4-tert cI NH I butylphenyl)sulfonyl]amino 0=S=0 }-4,5- Method A dichlorophenyl)thiophene 2-sulfonamide CH CH 3 62 0 s O= CI NH a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen O=s=o yl}-1,3-benzothiazole-6 sulfonamide S N 63 0 s O=s CI NH N-(4,5-dichloro-2-{[(2 CI NH chloro-4 I fluorophenyl)sulfonyl]amin Method A 0=s=0 o}phenyl)thiophene-2 CI sulfonamide F 64 0 s o=s-G CI NH : NH N-{4,5-dichloro-2-[(2 SNH thienylsulfonyl)amino]phen Method A CI yl}-1 H-1,2,4-triazole-5 o=s=o sulfonamide
N
7 NH 109 WO 2012/082633 PCT/US2011/064441 65 o s O=S CI N H a NH 2-chloro-N-{4,5-d ichloro-2 CI NH [(2 o=s=o thienylsulfonyl)amino]phen Method A yl}-1,3-benzothiazole-6 sulfonamide S C N CI 66 o S O=s CI NH N-(4,5-dichloro-2-{[(3,4 CI NH dimethylphenyl)sulfonyl]a Method A O=s=o mino}phenyl)thiophene-2 sulfonamide 67 0 o=s CI NH C : a NH N-(4,5-dichloro-2-{[(2,4 C NH dimethoxyphenyl)sulfonyl] Method A 0=b=0 amino}phenyl)thiophene 2-sulfonamide 110 WO 2012/082633 PCT/US2011/064441 68 o s O=s CI N H N-(4,5-d ichloro-2-{[(2,5 dichloro-3 CI NH thienyl)sulfonyl]amino}phe Method C o=s=o nyl)thiophene-2 sulfonamide CI 69 o S O=s CI NH N-(4,5-dichloro-2-{[(3 CI NH methoxyphenyl)sulfonyl]a Method A I mino}phenyl)thiophene-2 sulfonamide 70 0 s 0=s CI NH CI a NH N-[4,5-dichloro-2-({[4 CI NH (trifluoromethyl)phenyl]sulf Method C o=s=o onyl}amino)phenyl]thiophe ne-2-sulfonamide
CF
3 71 0 o CI NH a NH N-(4,5-dichloro-2-{[(3,4 CINH dichlorophenyl)sulfonyl]am o=s=o ino}phenyl)thiophene-2 sulfonamide CI 111 WO 2012/082633 PCT/US2011/064441 72 0 s o= CI N H N-[4,5-dichloro-2-({[3 CI NH (methylsulfonyl)phenyl]sulf Method A I onyl}amino)phenyl]thiophe 0=S=o ne-2-sulfonamide S 02 73 0 s II O=s II NH 1 CIa NH N-(4,5-dichloro-2-{[(3 chloro-2 CI NH methylphenyl)sulfonyl]ami Method A I no}phenyl)thiophene-2 sulfonamide CI 74 0 s O=S CI NH CI NH 3-{4-[({4,5-dichloro-2-[(2 o=s=o thienylsulfonyl)amino]phen Method B yl}amino)sulfonyl]phenyl}p ropanoic acid COOH 112 WO 2012/082633 PCT/US2011/064441 75 0 s CI NH CI NH 5-[({4,5-dichloro-2-[(2 O thienylsulfonyl)amino]phen Method B yl}amino)sulfonyl]-2 ethoxybenzoic acid COOH ro 76 0 0=8 CI NH CI NH N-{4-[({4,5-dichloro-2-[(2 0=S=0 thienylsulfonyl)amino]phen Method A yl}amino)sulfonyl]-2 methylphenyl}acetamide o NH 77 0 s 0=8 CI NH C ::a NHN-[2-({[3,5 bis(trifluoromethyl)phenyl] CI NH sulfonyl}amino)-4,5- Method C 0=S=0 dichlorophenyl]thiophene 2-sulfonamide
F
3 C C 1F 3 113 WO 2012/082633 PCT/US2011/064441 76 o s o:=s G CI N H N-{4,5-dichloro-2-[(2 C NH thienylsulfonyl)amino]phen Method C II yl}-1 H-pyrazole-4 o=s=o sulfonamide HN-N 77 0 s o:=s G CI NH N-(4,5-dichloro-2-{[(3 CI NH chlorophenyl)sulfonyl]amin Method A o}phenyl)thiophene-2 O=s=0 sulfonamide 78 0 s o:=s c CI NH CI NH N-[4,5-dichloro-2-({[4 I (trifluoromethoxy)phenyl]s O=s=S ulfonyl}amino)phenyl]thiop Method C hene-2-sulfonamide
_OCF
3 114 WO 2012/082633 PCT/US2011/064441 79 0 s 11 0=8 CI NH CI N H I= = N-[2-({[4 (benzyloxy)phenyl]sulfonyl }amino)-4,5- Method A dichlorophenyl]thiophene 2-sulfonamide 0 80 0 s O=s C I N H1 CI a NH N-(4,5-dichloro-2-{[(2 CI NH fluorophenyl)sulfonyl]amin Method A o}phenyl)thiophene-2 0=b=0 sulfonamide F 81 0 CI NH 2-chloro-5-[({4,5-dichloro CI NH I thienylsulfonyl)amino]phen Method B o=s=o yl}amino)sulfonyl]-4 F fluorobenzoic acid COOH CI 115 WO 2012/082633 PCT/US2011/064441 82 o s O=S CI N H methyl 5-chloro-3-[({4,5 CI NH dichloro-2-[(2 C thienylsulfonyl)amino]phen Method A o=s=o yl}amino)sulfonyl]thiophen e-2-carboxylate MeOOC SI CI 83 0 s 0=s 1 - I CI NH 3-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method B I yl}amino)sulfonyl]-4 0=S=0 fluorobenzoic acid F COOH 84 0 s 11 o=S CI NH CI NH 2-chloro-N-{4,5-dichloro-2 O=b=0 [(2- .Method C thienylsulfonyl)amino]phen yl}quinoline-6-sulfonamide CI 85 0 o O=S CI NH N-(4,5-dichloro-2-{[(5 chloro-2 CI NH fluorophenyl)sulfonyl]amin Method A o=s=o o}phenyl)thiophene-2 F sulfonamide C1 116 WO 2012/082633 PCT/US2011/064441 86 0 s 0=S CI N H NH N-{4,5-dichloro-2-[(2,3 CINH dihydro-1 H-inden-5 o=s=o ylsulfonyl)amino]phenyl}thi Method A ophene-2-sulfonamide 87 o S CI NH NH N-(4,5-dichloro-2-{[(4 CI NH chlorophenyl)sulfonyl]amin Method A o=s=o o}phenyl)thiophene-2 sulfonamide CI 88 o s CI NH N-{4,5-dichloro-2-[(1 CI NH naphthylsulfonyl)amino]ph Method A enyl}thiophene-2 0=S=0 sulfonamide 89 0 s 11 O=S CI NH a NH N-{4,5-dichloro-2-[(2 CINH thienylsulfonyl)amino]phen o=s=o yl}-1,3-benzodioxole-5 sulfonamide 10 117 WO 2012/082633 PCT/US2011/064441 90 0 s CI NH N-[4,5-dichloro-2-({[2 CI NH (trifluoromethoxy)phenyl]s Method A I ulfonyl}amino)phenyl]thiop 0=s=o hene-2-sulfonamide
F
3 C 91 0I O=S CI NH N-(4,5-dichloro-2-{[(3,5 dichloro-2 NH hydroxyphenyl)sulfonyl]am Method A o=s=o ino}phenyl)thiophene-2 HO sulfonamide C I I CI NH NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A o=s=o yl}-1 -benzofuran-5 sulfonamide 93 0 s I I o=s CI NH N-(4,5-dichloro-2-{[(2,6 CI NH dimethylphenyl)sulfonyl]a Method A mino}phenyl)thiophene-2 0=S=0 sulfonamide 118 WO 2012/082633 PCT/US2011/064441 94 0 s 11 O=S CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method A o=,s=o yl}quinoline-3-sulfonamide Nr 95 0 s 11 O-=So CI NH N-(4,5-dichloro-2-{[(2,3 CI NH dichlorophenyl)sulfonyl]am Method A s ino}phenyl)thiophene-2 ci= sulfonamide CID 96 II CI NH methyl 4-[({4,5-dichloro-2 CINH [(2 C thienylsulfonyl)amino]phen Method A O=s=U yl}amino)sulfonyl]benzoat e COOMe 97 0 s II O=s CI NH NH N-{4,5-dichloro-2-[(2 CINH thienylsulfonyl)amino]phen Method A 0=s=o yl}quinoline-8-sulfonamide 119 WO 2012/082633 PCT/US2011/064441 98 s CI a NH N-(4,5-dichloro-2-{[(2 CI NH chlorophenyl)sulfonyl]amin Method A o}phenyl)thiophene-2 o=s=o sulfonamide cl 99 0 s 11 O=s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A yl}-2,4-dimethyl-1,3 0=S= thiazole-5-sulfonamide
--
N 100 0 s O=s CI NH N-(4,5-dichloro-2-{[(3 CI NH chloro-4 I fluorophenyl)sulfonyl]amin Method D 0=6=U o}phenyl)thiophene-2 sulfonamide F 101 0 s 11 O=s CI NH N-{5-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phen CI NH yl}amino)sulfonyl]-4- Method A o=s=o methyl-1,3-thiazol-2 yl}acetamide 120 WO 2012/082633 PCT/US2011/064441 102 I s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A yl}isoquinoline-5 0=S=0 sulfonamide 103 0 s 11 O=s c CI NH NH 5-chloro-N-{4,5-dichloro-2 CI N [(2 o=s=o thienylsulfonyl)amino]phen Method A N yl}quinoline-8-sulfonamide c 1 CI 105 s O=S CI NH N-(4,5-dichloro-2-{[(2,5 NH dichlorophenyl)sulfonyl]am Method A I ino}phenyl)thiophene-2 0=S=0 sulfonamide CIC 106 0 s 11 o=si CI NH a NH N-(4,5-dichloro-2-{[(2,4,5 CI NH trifluorophenyl)sulfonyl]am o=s=o ino}phenyl)thiophene-2 F sulfonamide F F 121 WO 2012/082633 PCT/US2011/064441 107 0 s 11 CI N H a NH N-(4,5-dichloro-2-{[(3,4 CI NH dimethoxyphenyl)sulfonyl] o=s=o amino}phenyl)thiophene 2-sulfonamide OMe OMe 108 s o=s y CI NH CNH N-(4,5-dichloro-2-{[(2 CI NH methoxyphenyl)sulfonyl]a Method A mino}phenyl)thiophene-2 O=s=0 sulfonamide OMe 109 S o:=s CI NH CI NH N-[4,5-dichloro-2-({[3 I (difluoromethoxy)phenyl]s O=s=S ulfonyl}amino)phenyl]thiop Method A hene-2-sulfonamide Ob F F 110 0 s 0=s CI NH methyl 3-[({4,5-dichloro-2 [(2 CI NH thienylsulfonyl)amino]phen Method A I yl}amino)sulfonyl]thiophen O=s=U e-2-carboxylate 6.- COOMe 122 WO 2012/082633 PCT/US2011/064441 111 0 s 0=8 CI NH N-(4,5-d ichloro-2-{[(2,5 CI NH difluorophenyl)sulfonyl]ami Method A no}phenyl)thiophene-2 O==o sulfonamide F F F 112 0 s o=S CI NH N-{4,5-dichloro-2-[(2 NH thienylsulfonyl)amino]phen Method A CI yl}-3,5-dimethyl-1H 0=s=0 pyrazole-4-sulfonamide N-NH 113 0 s O=s CI NH a NH N-(4,5-dichloro-2-{[(2,4 CI NH difluorophenyl)sulfonyl]ami o=s=o no}phenyl)thiophene-2 F sulfonamide F 114 0 s 114 S II o=Si CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method A 0=8=0 yl}quinoline-6-sulfonamide 23N 123 WO 2012/082633 PCT/US2011/064441 115 0 s 11 o=s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen O=s=0 yl}-1 -(phenylsulfonyl)-1 H pyrrole-3-sulfonamide N "02 116 0 s O=s CI NH N-(4,5-dichloro-2-{[(3,5 CI NH dimethylphenyl)sulfonyl]a Method A mino}phenyl)thiophene-2 0=S=0 sulfonamide 117 0 s O=s CI NH N-(4,5-dichloro-2-{[(4 CI NH methoxy-3 I methylphenyl)sulfonyl]ami Method A O~b~unolphenyl)thiophene-2 sulfonamide 118 o S O=s CI NH N-(4,5-dichloro-2-{[(3 CI NH chloro-4 I methoxyphenyl)sulfonyl]a Method A mino}phenyl)thiophene-2 sulfonamide CI 124 WO 2012/082633 PCT/US2011/064441 119 o s O=s CI NH N-{4,5-dichloro-2-[(2 NH thienylsulfonyl)amino]phen Method A CI yl}-1 -methyl-1 H-pyrazole o=s=o 5-sulfonamide N 120 0 s O=s CI NH CI NH 1 -acetyl-N-{4,5-dichloro-2 1 [(2 thienylsulfonyl)amino]phen Method A yl}indoline-5-sulfonamide N COMe 121 0 s o=s CI NH a NH N-[4,5-dichloro-2-({[3-(5 CINH methyl- 1,3,4-oxadiazol-2 o=s= yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N N 125 WO 2012/082633 PCT/US2011/064441 122 0 s O=s CI NH a NH N-[4,5-dichloro-2-({[3-(l CI NH methyl-1 H-pyrazol-3 o=s=o yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N-N 123 0 s O=s CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method A yl}-4-methyl-2-phenyl-1,3 S Ythiazole-5-sulfonamide eN 124 0 s O=s CI NH a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-1-benzofuran-2 sulfonamide 126 WO 2012/082633 PCT/US2011/064441 125 0 o o=S CI N H NH 5-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}amino)sulfonyl]-2 methylbenzoic acid HOOC 126 0 s 0=8 CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen 0=S=0 yl}-2-oxo-1,2,3,4- Method C tetrahydroquinoline-6 sulfonamide NH 0 127 0 o O=s CI NH CI NH N-{4,5-dichloro-2-[(2 o=s=o thienylsulfonyl)amino]phen Method A yl}-2-oxo-2H-chromene-6 sulfonamide O 0 127 WO 2012/082633 PCT/US2011/064441 128 0 s 0=S CI NH CI NH N-{4,5-dichloro-2-[(2 O=S=O thienylsulfonyl)amino]phen Method C yl}-6-phenylpyridine-3 sulfonamide N 129 o s CI NH ethyl 3-[({4,5-dichloro-2 [(2 CI NH thienylsulfonyl)amino]phen Method A _ _yl}amino)sulfonyl]isonicoti nate COGOt NJ 130 0 s 0=S CI NH N-[4,5-dichloro-2-({[2 CI NH chloro-4 I (trifluoromethyl)phenyl]sulf Method C 0=6=0 onyl}amino)phenyl]thiophe CI ne-2-sulfonamide
CF
3 128 WO 2012/082633 PCT/US2011/064441 131 0 s 13 o=s CI N H a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-2,3-dihydro-1 benzofuran-5-sulfonamide 132 0 o O=S CI NH CI NH N-{4,5-dichloro-2-[(2 o=s=o thienylsulfonyl)amino]phen Method A yl}-6-phenoxypyridine-3 sulfonamide NJ 133 o s o=si CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method C 0=6=0 yl}-5-phenylthiophene-2 sulfonamide 129 WO 2012/082633 PCT/US2011/064441 134 o S o=S CI N H 3-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method B I yl}amino)sulfonyl]-4 0=S=0 methylbenzoic acid HOOC 135 0 s 11 o=~ II N H1 CI :NH N-(4,5-dichloro-2-{[(2,5 dimethyl-3 C NH thienyl)sulfonyl]amino}phe Method A o=s=o nyl)thiophene-2 sulfonamide S 136 0 s 11 o=~ CI NH CI NH N-{2-chloro-4-[({4,5 I dichloro-2-[(2 0=s=o thienylsulfonyl)amino]phen Method C yl}amino)sulfonyl]phenyl}a cetamide CI HN 0 137 0 s 0=8 CI NH N-(4,5-dichloro-2-{[(5 CI NH chloro-2,4 I difluorophenyl)sulfonyl]ami Method C O=s=U no}phenyl)thiophene-2 F sulfonamide CI F 130 WO 2012/082633 PCT/US2011/064441 138 o s o= CI NH CI NH N-[4,5-dichloro-2-({[4-(l = methyl-1 H-pyrazol-3 yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N N 139 0 s o=S CI NH a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-5-methyl-1- Method A benzothiophene-2 S sulfonamide 140 0 S 0=S CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A I yl}-2,5-dimethylfuran-3 0S==0 sulfonamide 131 WO 2012/082633 PCT/US2011/064441 141 O s O=s CI NH NH N-[4,5-dichloro-2-({[4 CI NH (pyrrolidin-1 o=s=o ylsulfonyl)phenyl]sulfonyl} Method C amino)phenyl]thiophene 2-sulfonamide
OCN-SO
2 142 I S O=s CI NH methyl 5-[({4,5-dichloro-2 NH [(2 CI thienylsulfonyl)amino]phen Method C o=s= yl}amino)sulfonyl]-2 methyl -3-furoate COOMe 143 0 s O=S CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen I yl}-3-oxo-3,4-dihydro-2H- Method A 1,4-benzoxazine-6 sulfonamide NH 0 132 WO 2012/082633 PCT/US2011/064441 144 0 O O=S CI N H 2,4-dichloro-5-[({4,5 CI NH dichloro-2-[(2 I thienylsulfonyl)amino]phen Method B 0=6=U yl}amino)sulfonyl]benzoic C1 acid HO o CI 145 0 O O=s CI NH CI NH N-[4,5-dichloro-2-({[4 o=s=o (difluoromethoxy)phenyl]s Method A ulfonyl}amino)phenyl]thiop hene-2-sulfonamide F 0 F 146 o s O=S CI NH N-(4,5-dichloro-2-{[(5 NH {[(dimethylamino)carbonyl] O=s=o amino}-2- Method A ethoxyphenyl)sulfonyl]ami no}phenyl)thiophene-2 CH3 Hsulfonamide O '- N -CH3 CH;H3 133 WO 2012/082633 PCT/US2011/064441 147 o s O= CI N H a NH N-{5-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}amino)sulfonyl]-2 methoxyphenyl}acetamide HN OMe 148 0 s CI NH 6-chloro-N-{4,5-dichloro-2 [(2 CI NH thienylsulfonyl)amino]phen Method C I yl}imidazo[2,1 O=b=0 b][1,3]thiazole-5 CI N sulfonamide N S 149 0 s CI NH N-[4,5-dichloro-2-({[3-(1 CI NH methyl-1 H-pyrazol-5 _ yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N.--N 150 0 s 11 CI NH methyl 5-[({4,5-dichloro-2 [(2 CI NH thienylsulfonyl)amino]phen Method A _ _yl}amino)sulfonyl]-1 OSO~ methyl-1 H-pyrrole-2 -N -carboxylate MeOOC 134 WO 2012/082633 PCT/US2011/064441 151 0 s 11 O=S CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A yl}-5-methylfuran-2 0=3=0 sulfonamide 152 0 S 11 CI NH CI NH 0=S=0 N-[4,5-dichloro-2-({[4 (phenoxymethyl)phenyl]su Method A Ifonyl}amino)phenyl]thioph ene-2-sulfonamide 0 153 0 s II O=S CI NH CI NH N-(4,5-dichloro-2-{[(4 0=S=0 phenoxyphenyl)sulfonyl]a Method A mino}phenyl)thiophene-2 sulfonamide 0 135 WO 2012/082633 PCT/US2011/064441 154 o s O= CI N H NH 5,6-dichloro-N-{4,5 CI NH dichloro-2-[(2 o=s=o thienylsulfonyl)amino]phen yl}pyridine-3-sulfonamide CI N CI 155 0 s 11 O=S CI NH N-(4,5-dichloro-2-{[(2 CI NH fluoro-4 I methylphenyl)sulfonyl]ami Method A 0=S=0 no}phenyl)thiophene-2 F sulfonamide 0 1 156 0 s O=S CI NH N-(4,5-dichloro-2-{[(2 CI NH ethoxy-5 _ f[(methylamino)carbonyl]a Method A 0=S=0 ~minolphenyl)sulfonyl]amin Mto o}phenyl)thiophene-2 sulfonamide NH 136 WO 2012/082633 PCT/US2011/064441 157 0 s 11 O=S CI NH CI NH N-{4,5-dichloro-2-[(2 O== thienylsulfonyl)amino]phen Method A yl}-6-morpholin-4 ylpyridine-3-sulfonamide N 158 o s o=s CI NH CI NH N-{4,5-dichloro-2-[({3-[(6 o=s=o methylpyrazin-2 yl)oxy]phenyl}sulfonyl)ami Method A no]phenyl}thiophene-2 sulfonamide 0 N N
CH
3 159 s CI NH CI :NH N-{4,5-dichloro-2-[(2 C NH thienylsulfonyl)amino]phen Method A O=S=0 yl}chromane-6 sulfonamide 0 137 WO 2012/082633 PCT/US2011/064441 160 o s o=s-G CI N H CI NH N-[4,5-dichloro-2-({[4-(3,5 O=S=O dimethyl-1 H-pyrazol-1 yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N
CH
3 N
CH
3 161 o s o=s-G CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A I ~ yl}-5-methylthiophene-2 0S0= sulfonamide s 162 o s o=s-G CI NH NH 5-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen O=8=0 yl}amino)sulfonyl]-2 hydroxybenzoic acid HOOC 138 WO 2012/082633 PCT/US2011/064441 163 o s o=s CI NH a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method C 0=s= yl}- 1 -benzothiophene-2 sulfonamide s 164 0 s 11 O:=sG CI NH N-(4,5-dichloro-2-{[(2,4 CI NH dichloro-5 I methylphenyl)sulfonyl]ami Method A 0=s=0 no}phenyl)thiophene-2 CI sulfonamide CI 165 o s oh CI NH N-[4,5-dichloro-2-({[4 CI NH fluoro-3 I (trifluoromethyl)phenyl]sulf Method C 0=6=U onyl}amino)phenyl]thiophe ne-2-sulfonamide
F
3 C F 166 0 s 0=s II NH CI :NH methyl 3-[({4,5-dichloro-2 [(2 CI NH thienylsulfonyl)amino]phen Method C o=s=o yl}amino)sulfonyl]benzoat e COOMe 139 WO 2012/082633 PCT/US2011/064441 167 o S o=s CI N H methyl 5-[({4,5-dichloro-2 CI NH [(2 = thienylsulfonyl)amino]phen Method C yl}amino)sulfonyl]-4 0 / s methoxythiophene-3
CH
3 carboxylate 0 0
CH
3 168 0 s o=s; y CI NH methyl 5-[({4,5-dichloro-2 NH[(2 CI thienylsulfonyl)amino]phen Method C o=s=o yl}amino)sulfonyl]-2 furoate COOMe 169 0 s O:=sG CI NH a NH N-(4,5-dichloro-2-{[(2 CI NH chloro-4 O=S=O cyanophenyl)sulfonyl]amin Method C C1 o}phenyl)thiophene-2 sulfonamide || N 140 WO 2012/082633 PCT/US2011/064441 170 0 s 11 O=s CI N H N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A yl}l-1 -methyl-1 H-pyrazole 3-sulfonamide N N
CH
3 171 0 s o=s CI NH N-{4,5-dichloro-2-[(2 cI NH thienylsulfonyl)amino]phen Method A C Nyl}-l -methyl-1 H-indole-7 0=S= CH 3 sulfonamide N 172 0 s 11 0==S c CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method A 0S=O yl}-5-pyridin-2 s ylthiophene-2-sulfonamide N 141 WO 2012/082633 PCT/US2011/064441 173 0 s O=S CI NH CI N H o=s=o N-(4,5-dichloro-2-{[(4' fluorobiphenyl-4- Method A yl)sulfonyl]amino}phenyl)t hiophene-2-sulfonamide F 174 0 s CI NH a NH N-(4,5-dichloro-2-{[(3 CI NH fluoro-4 o=s=o methoxyphenyl)sulfonyl]a Method A mino}phenyl)thiophene-2 sulfonamide F CH3 175 0 s CI NH N-(4,5-dichloro-2-{[(3 chloro-2 C NH fluorophenyl)sulfonyl]amin Method C o=s=o o}phenyl)thiophene-2 F sulfonamide 142 WO 2012/082633 PCT/US2011/064441 176 0 s CI N H a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-2-oxo-2,3-dihydro-1,3- Method A benzothiazole-6 sulfonamide s 0 NH 177 0 s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A yl}furan-3-sulfonamide 6 178 0 s CI NH CI NH N-[4,5-dichloro-2-({[3-(5 I methyl- 1,2,4-oxadiazol-3 0=S=0 yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N N
CH
3 143 WO 2012/082633 PCT/US2011/064441 179 o s o=s-G CI NH CI NH ethyl 5-[({4,5-dichloro-2 1 ~ ~ [(2 0=S=0 thienylsulfonyl)amino]phen Method C yl}amino)sulfonyl]-3 furoate =0 0 180 o s O=s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-3,4-dihydro-2H-1,5- Method A benzodioxepine-7 sulfonamide 0 0 181 0 s 0==S c CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A yl}-2,3-dihydro-1 O== benzofuran-7-sulfonamide 0 144 WO 2012/082633 PCT/US2011/064441 182 o s o=s-G CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen O=S=0 yl}-2-methyl-1,3- Method A benzothiazole-6 sulfonamide S N 183 o s o=s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A I~so yl}-1,3,5-trimethyl-1H 0=S=0pyrazole-4-sulfonamide
CH
3 /
CH
3 N-N
CH
3 184 s S o=s-G CI NH N-(4,5-dichloro-2-{[(4 CI NH chloro-2 I fluorophenyl)sulfonyl]amin Method C 0=s=0 o}phenyl)thiophene-2 F sulfonamide CI 185 o s O=S CI NH N-(4,5-dichloro-2-{[(3 CI NH cyano-4 I fluorophenyl)sulfonyl]amin Method C 0=S=0 o}phenyl)thiophene-2 sulfonamide N F 145 WO 2012/082633 PCT/US2011/064441 186 o s o=s-G CI NH CI NH N-{5-[({4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method A yl}amino)sulfonyl]-1,3 S thiazol-2-yl}acetamide -N HN
CH
3 187 o s O= CI NH C NN-{4,5-dichloro-2-[({4-[(6 0=s=U methylpyrazin-2 yl)oxy]phenyl}sulfonyl)ami Method A no]phenyl}thiophene-2 sulfonamide N
CH
3 188 o S O=S CI NH N-(4,5-dichloro-2-{[(3 CI NH pyrimidin-2 _ ylphenyl)sulfonyl]amino}ph Method A enyl)thiophene-2 sulfonamide N 14N 146 WO 2012/082633 PCT/US2011/064441 189 0 s 0=S methyl 3-[({4,5-dichloro-2 [(2 CI NH thienylsulfonyl)amino]phen Method A o=s=0 yl}amino)sulfonyl]-4 methoxybenzoate MeO or COOMe 190 0 s 11 O=s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A I yl}-1 -benzothiophene-3 0=s=o sulfonamide 7 191 0 s 11 O=s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen yl}-4-methyl-3,4-dihydro 0S0~u 2H-pyrido[3,2- Method A b][1,4]oxazine-7 sulfonamide N
CH
3 192 s S o=s CI NH 5-chloro-N-{4,5-dichloro-2 NH [(2 CI thienylsulfonyl)amino]phen Method A O=S=O yl}-1,3-dimethyl-1 H CI
CH
3 pyrazole-4-sulfonamide N-N CH3 147 WO 2012/082633 PCT/US2011/064441 193 o s O=S CI N H N-{4,5-dichloro-2-[(3 NH thienylsulfonyl)amino]phen Method A CI yl}thiophene-2 o=s=o sulfonamide 6 194 0 s 11 O=S CI NH N-(4,5-dichloro-2-{[(5 CI NH chloro-2 o=s=o naphthyl)sulfonyl]amino}p Method A henyl)thiophene-2 sulfonamide CI 195 0 s O=s CI NH NH N-{2-[(biphenyl-3 CI NH ylsulfonyl)amino]-4,5 0=S=0 dichlorophenyl}thiophene 2-sulfonamide 196 o s II NH1 CI :NH N-(4,5-dichloro-2-{[(2 fluoro-5 CI NH methylphenyl)sulfonyl]ami Method A o=s=o no}phenyl)thiophene-2 F sulfonamide
CH
3 148 WO 2012/082633 PCT/US2011/064441 197 o s O=s CI N H 4-chloro-3-[({4,5-dichloro CI NH 2-[(2 1 thienylsulfonyl)amino]phen Method A 0S0~ yl}amino)sulfonyl]benzoic CI acid HO 0 198 s S CI NH 3-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method B yl}amino)sulfonyl]-4 O=00 methoxybenzoic acid OMe HOOC 199 o S O=s CI NH CI NH N-[4,5-dichloro-2-({[4 I (pyridin-2 yloxy)phenyl]sulfonyl}amin Method C o)phenyl]thiophene-2 sulfonamide 10 I N 149 WO 2012/082633 PCT/US2011/064441 200 O s o=s11 CI N H CI a NH N-{4,5-dichloro-2-[(2 C NH naphthylsulfonyl)amino]ph Method C 0=S=0 enyl}thiophene-2 sulfonamide 201 0 s 11 O=S CI NH NH 3-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}amino)sulfonyl]benzoic acid OH 0 202 0 s O=s CI NH CI NH N-[4,5-dichloro-2-({[6 o=s=o (dimethylamino)-2 naphthyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide CH3 1CH3 150 WO 2012/082633 PCT/US2011/064441 203 o s o= CI N H CI a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A I= yl}pyridine-3-sulfonamide N6 204 0 s 11 O=S CI NH CI NH o=s=o N-(4,5-dichloro-2-{[(4' chlorobiphenyl-4- Method A yl)sulfonyl]amino}phenyl)t hiophene-2-sulfonamide CI 205 0 s O=S CI NH Cl~ aNHN-(2-{[(3 CI NH acetylphenyl)sulfonyl]amin o}-4,5- Method A O=s=o dichlorophenyl)thiophene 2-sulfonamide 0 CH3 151 WO 2012/082633 PCT/US2011/064441 206 o S o=s CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen O=s=0 yl}-2,3-dioxo-1,2,3,4- Method A tetrahydroquinoxaline-6 sulfonamide NH HN O 207 0I O=S CI NH CI NH N-{4-[({4,5-dichloro-2-[(2 O==O thienylsulfonyl)amino]phen Method A yl}amino)sulfonyl]benzyl}a cetamide HN 0
CH
3 208 0 s O=s CI NH N-[4,5-dichloro-2-({[3 CI NH (trifluoromethyl)phenyl]sulf Method C I onyl}amino)phenyl]thiophe 0=S=0 ne-2-sulfonamide
F
3 C 152 WO 2012/082633 PCT/US2011/064441 209 o S O=S CI N H N-[4,5-dichloro-2-({[2 CI NH (methylsulfonyl)phenyl]sulf Method E I onyl}amino)phenyl]thiophe 0=0 0 ne-2-sulfonamide \ CH 3 s 210 0 s 11 o=s CI NH N-{4,5-d ich loro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A yl}-3-methylquinoline-8 o=s=0 sulfonamide N l
CH
3 211 0 s o=S3 CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen I yl}-2,3-dihydro-1,4- Method A O~b~ubenzodioxine-6 sulfonamide 212 o S O=S CI NH CI NH N-[4,5-dichloro-2-({[3-(2 I methylpyrimidin-4 0=s=o yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N N
CH
3 153 WO 2012/082633 PCT/US2011/064441 213 o S O=S CI NH a NH 6-chloro-N-{4,5-dichloro-2 CI N [(2 o=s=0 thienylsulfonyl)amino]phen Method C yl}pyridine-3-sulfonamide N CI 214 o s CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method A 0=S=0 yl}-6-methoxypyridine-3 sulfonamide N 0 CH3 215 0I O=S CI NH methyl 5-[({4,5-dichloro-2 CI NH [(2 1 thienylsulfonyl)amino]phen Method A yl}amino)sulfonyl]-2 methylbenzoate O CH3
CH
3 0 216 0 s O=S CI NH N-(4,5-dichloro-2-{[(2,5 CI NH dimethoxyphenyl)sulfonyl] Method A amino}phenyl)thiophene 0=S=0 2-sulfonamide
CH
3 CH3 154 WO 2012/082633 PCT/US2011/064441 217 0 s O= CI N H C ::a NHN-(2-{[(4 CI NH acetylphenyl)sulfonyl]amin o}-4,5- Method A 0=6=U dichlorophenyl)thiophene 2-sulfonamide COMe 218 o s o=s-G CI NH methyl 3-[({4,5-dichloro-2 CI NH [(2 0=S=0 thienylsulfonyl)amino]phen Method A CH3 yl}amino)sulfonyl]-2
H
3 methylbenzoate .0
CH
3 219 0 s CI NH CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method C yl}-5-isoxazol-5 S ylthiophene-2-sulfonamide N 155 WO 2012/082633 PCT/US2011/064441 220 0 s o=si CI N H a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-5-(1,3-oxazol-5- Method C yl)thiophene-2 s sulfonamide N lO 221 0 s O=S II N H1 CI :NH N-(4,5-dichloro-2-{[(5 chloro-2 CI NH methylphenyl)sulfonyl]ami Method A o=s=o no}phenyl)thiophene-2 sulfonamide
CH
3 CI 222 o S o=s CI NH N-[4,5-dichloro-2-({[5 CI NH (dimethylamino)-1 os=o naphthyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N
CH
3 , CH 3 223 0 s 0S CI NH methyl 2-[({4,5-dichloro-2 [(2 Ci NH thienylsulfonyl)amino]phen Method A o=s=o yl}amino)sulfonyl]-4 EtOOC methoxybenzoate 156 WO 2012/082633 PCT/US2011/064441 224 o s o=S; CI NH 5-chloro-N-{4,5-dichloro-2 NH[(2 CI thienylsulfonyl)amino]phen Method C o=s=o yl}thiophene-2 sulfonamide S CI 225 o s o=s-G CI NH CI NH N-(4,5-dichloro-2-{[(4 I_ pyrimidin-2 ylphenyl)sulfonyl]amino}ph Method A enyl)thiophene-2 sulfonamide Nf N 226 o s O=S CI NH N-{4,5-dichloro-2 [(methylsulfonyl)amino]ph Method E NH enyl}thiophene-2 CI sulfonamide o=s=o
CH
3 227 0 s O=S CI NH N-(4,5-dichloro-2-{[(3,5 Cl NH dichloro-4 I hydroxyphenyl)sulfonyl]am Method A 0=6=0 ino}phenyl)thiophene-2 sulfonamide Cl Cl OH 157 WO 2012/082633 PCT/US2011/064441 228 o S CI NH N-[4,5-dichloro-2-({[4 CI NH chloro-3 I (trifluoromethyl)phenyl]sulf Method C 0=S=0 onyl}amino)phenyl]thiophe ne-2-sulfonamide
CF
3 CI 229 0 s O=S CI NH 2-chloro-5-[({4,5-dichloro CI NH 2-[(2 1 thienylsulfonyl)amino]phen Method B yl}amino)sulfonyl]benzoic acid o OH CI 230 o S o=~ CI NH CI NH N-[4,5-dichloro-2-({[4 I (pyridin-3 yloxy)phenyl]sulfonyl}amin Method C o)phenyl]thiophene-2 sulfonamide 01 N 158 WO 2012/082633 PCT/US2011/064441 231 o s o= CI N H N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A I_ _eyl}-l -methyl-1 H-imidazole 4-sulfonamide N N
CH
3 232 o s O=s CI NH N-{4,5-dichloro-2 [(ethylsulfonyl)amino]phen Method E CI NH yl}thiophene-2 sulfonamide o=s=o 233 I S O=S CI NH N-(4,5-dichloro-2-{[(4 CI NH chloro-2-fluoro-5 I methylphenyl)sulfonyl]ami Method C == no}phenyl)thiophene-2 F sulfonamide CI 234 0 s O=S CI NH NH 5-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}amino)sulfonyl]-2 fluorobenzoic acid COOH F 159 WO 2012/082633 PCT/US2011/064441 235 o s o=~ CI N H N-{2-[(biphenyl-2 cI NH ylsulfonyl)amino]-4,5- Method A C Ndichlorophenyl}thiophene o=s=o 2-sulfonamide 236 0 s 11 0==S c CI NH N-{3-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method A I yl}amino)sulfonyl]-4 0=s=0 methylphenyl}acetamide CH3
CH
3 N 237 0 s CI NH N-(2-{[(5-tert-butyl-2 CI NH methylphenyl)sulfonyl]ami no}-4,5- Method C 0=S=0 dichlorophenyl)thiophene
CH
3 2-sulfonamide
CH
3 tH3 238 I S 0=S I N-{2 CI NH [(benzylsulfonyl)amino] 4,5- Method E CI NH dichlorophenyl}thiophene 2-sulfonamide 0=1 11 0 160 WO 2012/082633 PCT/US2011/064441 239 0 s N-{4,5-dichloro-2 [(isobutylsulfonyl)amino]ph Method E CI NH enyl}thiophene-2 o=s=o sulfonamide 240 o s CI NH CI NH N-{4,5-dichloro-2-[(2 o=s=o thienylsulfonyl)amino]phen Method A yl}-2,2-dimethylchromane 6-sulfonamide 0
CH
3
CH
3 241 I S O=s CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method C I__ yl}-1,2-dimethyl-1
H
0=S=0imidazole-4-sulfonamide N N
CH
3
CH
3 161 WO 2012/082633 PCT/US2011/064441 242 o s 0=S CI N H a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=0 yl}-2-oxo-2,3,4,5- Method A tetrahydro-1 H-1 benzazepine-7 sulfonamide NH 0 243 0 s O=S CI NH CI NH N-(4,5-dichloro-2-{[(4 == cyclohexylphenyl)sulfonyl] Method A amino}phenyl)thiophene 2-sulfonamide 244 s S O s CI NH 4-chloro-N-1 -- {4,5 CI NH dichloro-2-[(2 thienylsulfonyl)amino]phen Method A yl}benzene-1,3 disulfonamide
SO
2
NH
2 162 WO 2012/082633 PCT/US2011/064441 245 o s O=s CI N H a NH N-(4,5-dichloro-2-{[(4 CI NH fluorophenyl)sulfonyl]amin 0=s=0 o}phenyl)thiophene-2 sulfonamide F 246 o S o=s CI NH a NH N-{3-[({4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen Method C o=s=o yl}amino)sulfonyl]phenyl}a cetamide N KCH 3 H 247 o s O= CI NH CI :NH N-{4,5-dichloro-2-[(2 C NH thienylsulfonyl)amino]phen Method o=s=o yl}-l -methyl-1 H-indole-4 sulfonamide N
CH
3 248 I s o:=s y CI NH N-(2-{[(4-bromo-3 CI NH methylphenyl)sulfonyl]ami no}-4,5- Method A O=s=U dichlorophenyl)thiophene 2-sulfonamide
CH
3 Br 163 WO 2012/082633 PCT/US2011/064441 249 s S o:=s y CI N H N-(4,5-dichloro-2-{[(3 CI NH chloro-4 I cyanophenyl)sulfonyl]amin Method C 0=s=U o}phenyl)thiophene-2 sulfonamide CI CN 250 o s O= CI NH NH N-{4,5-dichloro-2-[(5,6,7,8 CI NH tetrahydronaphthalen-2 0=S=0 ylsulfonyl)amino]phenyl}thi ophene-2-sulfonamide 251 o S o=s CI NH CI NH N-[4,5-dichloro-2-({[4-(2 O==0 chlorophenoxy)phenyl]sulf Method A onyl}amino)phenyl]thiophe ne-2-sulfonamide CI 0 164 WO 2012/082633 PCT/US2011/064441 252 o S o=s CI NH a NH N-(4,5-dichloro-2-{[(4 CI NH methoxyphenyl)sulfonyl]a Method A o=s=o mino}phenyl)thiophene-2 sulfonamide 253 s S o=s CI NH N-(4,5-dichloro-2-{[(2 CI NH methylphenyl)sulfonyl]ami Method A no}phenyl)thiophene-2 O=s=0 sulfonamide 254 s S o=s CI NH CI NH 2-{4-[({4,5-dichloro-2-[(2 O=s=0 thienylsulfonyl)amino]phen Method C yl}amino)sulfonyl]phenoxy }acetamide 0>
CONH
2 165 WO 2012/082633 PCT/US2011/064441 255 s S o:=s y CI N H a NH N-(4,5-dichloro-2-{[(2,4 CI NH dichlorophenyl)sulfonyl]am 0=s=0 ino}phenyl)thiophene-2 CI, sulfonamide CI 256 o s o= CI NH a NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-3,5-dimethyl-1 -phenyl- Method A 1 H-pyrazole-4 sulfonamide N-N b 257 I s o:=s y CI NH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen I_ _e yl}-4-methyl-3,4-dihydro- Method A O~b~u2H-1,4-benzoxazine-6 sulfonamide "N 0 258 0 s o:=s y CI NH 2-chloro-N-{4,5-dichloro-2 ClNH [(2- Mto I thienylsulfonyl)amino]phen Method A O=s=S yl}pyridine-3-sulfonamide CI 166 WO 2012/082633 PCT/US2011/064441 259 o s o=~ CI N H 4-acetyl-N-{4,5-dichloro-2 cI NH [(2 C thienylsulfonyl)amino]phen Method A 0=S=0 yl}-3,4-dihydro-2H-1,4 benzoxazine-6 sulfonamide N 260 I s o:=s y CI NH N-(4,5-dichloro-2-{[(2,6 CI NH difluorophenyl)sulfonyl]ami Method A no}phenyl)thiophene-2 O=s=S sulfonamide F F 261 0 0 CI NH N-{5-chloro-2-[(2 thienylsulfonyl)amino]phen Method A CI NH yl}-1-benzofuran-2 o=s=o sulfonamide 262 0 0 N H N-{4-chloro-2-[(2 thienylsulfonyl)amino]phen Method A CI NH yl}-1-benzofuran-2 o=s=o sulfonamide 167 WO 2012/082633 PCT/US2011/064441 263 0 o CI NH N-{5-chloro-2 [(methylsulfonyl)amino]ph Method A enyl}-1 -benzofuran-2 NH sulfonamide O=s=o 264 0 0 N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 NH chlorophenyl}-1 -methyl- Method A 1~ 1 H-imidazole-4 sulfonamide N N -/ 265 0 0 CI NHN-{2 [(benzylsulfonyl)amino]-5- Method A NH chlorophenyl}-1 o=s=o benzofuran-2-sulfonamide 266 0 o U=b II CI NH N-(5-chloro-2-{[(3 NH fluorophenyl)sulfonyl]amin Method A I o}phenyl)-1-benzofuran-2 O=S=0 sulfonamide F 168 WO 2012/082633 PCT/US2011/064441 267 0 0 CI NH C N XH N-(5-chloro-2-{[(4 NH fluorophenyl)sulfonyl]amin o=s=o o}phenyl)-1-benzofuran-2 sulfonamide F 268 0 o II CI NH N-(5-chloro-2-{[(3 NH cyanophenyl)sulfonyl]amin Method A I o}phenyl)-1 -benzofuran-2 0=S=0 sulfonamide CN 269 0 a CI NH N-(5-chloro-2-{[(4 NH methoxyphenyl)sulfonyl]a o=s=o mino}phenyl)-1 benzofuran-2-sulfonamide OMe 270 0 CI NH N-(5-chloro-2-{[(3 NH methoxyphenyl)sulfonyl]a Method A mino}phenyl)-1 O=s=0 benzofuran-2-sulfonamide __ __ _OMe 169 WO 2012/082633 PCT/US2011/064441 271 0 II CI NH N-(5-chloro-2-{[(3 NH chlorophenyl)sulfonyl]amin Method A I o}phenyl)-1 -benzofuran-2 0=s=O sulfonamide 272 0 o CI NH N-(5-chloro-2-{[(4 NH chlorophenyl)sulfonyl]amin o=s=o o}phenyl)-1-benzofuran-2 sulfonamide CI 273 o os CI NH : NH N-{5-chloro-2-[(2 I naphthylsulfonyl)amino]ph Method A 0=S=O enyl}-1 -benzofuran-2 sulfonamide 274 0 0 CI NH N-{2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4- Method A chlorophenyl}quinoline-8 ==0 sulfonamide N 170 WO 2012/082633 PCT/US2011/064441 275 0 0 II CI NH NH N-(5-chloro-2-{[(3,4 NH dimethoxyphenyl)sulfonyl] o=s=o amino}phenyl)-1 We benzofuran-2-sulfonamide OMe 276 0 11 U=b CI NH C *,N N -( 5 -c h lo r o -2 -{ [( 2 ,4 NH dichlorophenyl)sulfonyl]am Method A o=s=o ino}phenyl)-1 -benzofuran CI 2-sulfonamide CI 277 0 U=15 II CI NH NH N-{2-[(biphenyl-4 O=S=O ylsulfonyl)amino]-5- Method A chlorophenyl}-1 benzofuran-2-sulfonamide 171 WO 2012/082633 PCT/US2011/064441 278 0 o CI NH N H N-[5-chloro-2-({[4 NH (methylsulfonyl)phenyl]sulf Method A o=s=o onyl}amino)phenyl]-1 benzofuran-2-sulfonamide
SO
2 Me 279 0 0 o K CI NH N-(5-chloro-2-{[(4 NH methylphenyl)sulfonyl]ami Sno}phenyl)-1-benzofuran-Method A 2-sulfonamide 280 0 0 CI NH NH N-[5-chloro-2-({[4 NH (trifluoromethyl)phenyl]sulf Method A o=s=o onyl}amino)phenyl]-1 benzofuran-2-sulfonamide
CF
3 281 0 0 CI NH N-[5-chloro-2-({[4 NH (trifluoromethoxy)phenyl]s Method A o=s=o ulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide
OCF
3 172 WO 2012/082633 PCT/US2011/064441 282 0 0 CI NH N-{5-chloro-2-[(1 NH naphthylsulfonyl)amino]ph Method A enyl}-1-benzofuran-2 O=S=0 sulfonamide 283 0 0 o=s5 CI NH N-(5-chloro-2-{[(2 NH chlorophenyl)sulfonyl]amin Method A I o}phenyl)-1 -benzofuran-2 O=S=0 sulfonamide CI 284 0 o CI NH N-[5-chloro-2-({[3 NH (trifluoromethyl)phenyl]sulf Method A I onyl}amino)phenyl]-1 0=s=o benzofuran-2-sulfonamide
CF
3 285 0 0 II CI NH N-(5-chloro-2-{[(2 NH methoxyphenyl)sulfonyl]a Method A mino}phenyl)-1 0=S=o benzofuran-2-sulfonamide OMe 173 WO 2012/082633 PCT/US2011/064441 286 CI NH 0 N-(5-chloro-2-{[(3,5 NH difluorophenyl)sulfonyl]ami Method A no}phenyl)-1-benzofuran O=S=0 2-sulfonamide F F 287 O=S CI NH NH 0N-(5-chloro-2-{[(3,4 NH difluorophenyl)sulfonyl]ami o=s=o no}phenyl)-1-benzofuran 2-sulfonamide F F 288 C C - NH 0N-(2-{[(4-tert NH butylphenyl)sulfonyl]amino Method o=s=o }-5-chlorophenyl)-1 benzofuran-2-sulfonamide t-Bu 289 CI NH NH 0N-(5-chloro-2-{[(3,4 NH dichlorophenyl)sulfonyl]am o=s=o ino}phenyl)-1-benzofuran 2-sulfonamide CI 174 WO 2012/082633 PCT/US2011/064441 290 0 CI _NH 0 NH o=s= N-[2-({[4 (benzyloxy)phenyl]sulfonyl Method A }amino)-5-chlorophenyl]-1 benzofuran-2-sulfonamide 0 291 CI NH N-{2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4 chlorophenyl}-1,3- Method A 0=S=o benzodioxole-5 sulfonamide 40 0-] 292 0 CI NH N-{2-[(1 -benzofuran-2 ylsulfonyl)amino]-4 NH chlorophenyl}-2,4- Method A I dimethyl-1,3-thiazole-5 sulfonamide N 175 WO 2012/082633 PCT/US2011/064441 292 U=s CI NH N-[5-chloro-2-({[3 NH (difluoromethoxy)phenyl]s Method A ulfonyl}amino)phenyl]-1 0=s=O benzofuran-2-sulfonamide O F 293 0 CI NH N-(5-chloro-2-{[(3,5 NH dichlorophenyl)sulfonyl]am Method A I ino}phenyl)-1 -benzofuran 0=s=O 2-sulfonamide C1 CI 294 0 N-(5-chloro-2-{[(3 NH methylphenyl)sulfonyl]ami Method A no}phenyl)-1-benzofuran O=s=0 2-sulfonamide 295 CI NH 0 N-{5-chloro-2-[(2 furylsulfonyl)amino]phenyl Method A NH }-1-benzofuran-2 o=s=o sulfonamide 176 WO 2012/082633 PCT/US2011/064441 296 NH 0N -{2-[(1 -benzothien-3 NH ylsulfonyl)amino]-5 o=s=o chlorophenyl}-1 benzofuran-2-sulfonamide s 297 0 N-{2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4 chlorophenyl}-1,3- Method A O=S=0 benzothiazole-6 sulfonamide 4zN S-J 298 0 CI NH0 N-[5-chloro-2-({[3 NH (methylsulfonyl)phenyl]sulf Method A onyl}amino)phenyl]-1 0=s benzofuran-2-sulfonamide
CH
3 299 CI 0NH N-(5-chloro-2-{[(2 fluorophenyl)sulfonyl]amin Method A NH o}phenyl)-1-benzofuran-2 NH sulfonamide F 177 WO 2012/082633 PCT/US2011/064441 300 C1,,NH 0 CH3 CI NH 3 N-(5-chloro-2-{[(2,5 NH 0 dimethoxyphenyl)sulfonyl] Method A I -amino}phenyl)-1 o= benzofuran-2-sulfonamide 0
CH
3 301 0 CI NH N-[5-chloro-2-({[2 (trifluoromethoxy)phenyl]s Method A NH ulfonyl}amino)phenyl]-1 I -benzofuran-2-sulfonamide
F
3 CO 302 CI NH O N-(5-chloro-2-{[(5-chloro 0 2 thienyl)sulfonyl]amino}phe Method A NH cI nyl)-1-benzofuran-2 0I sulfonamide 303 CI N -~ N-(5-chloro-2-{[(3-chloro fluorophenyl)sulfonyl]amin Method A NH o}phenyl)-1-benzofuran-2 O=b F sulfonamide 304 1 methyl 3-[({2-[(1 benzofuran-2 NH ylsulfonyl)amino]-4- Method A 0=b chlorophenyl}amino)sulfon 0 yl]thiophene-2-carboxylate 0
CH
3 178 WO 2012/082633 PCT/US2011/064441 305 CI- NH 0 N-{5-chloro-2 [(ethylsulfonyl)amino]phen Method A yl}-l -benzofuran-2 NH sulfonamide o CH 3 306 CI NH N-{2-[(l-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-3,5- Method A NH dimethylisoxazole-4 o=sI sulfonamide 0 0 307 0 307H N-(5-chloro-2-{[(5-chloro CI NH 3-methyl-1 -benzothien-2 yl)sulfonyl]amino}phenyl)- Method A NH CI 1-benzofuran-2 s sulfonamide o s 3080 308NHCI N-(5-chloro-2-{[(2-chloro CI fluorophenyl)sulfonyl]amin Method A NH o}phenyl)-1 -benzofuran-2 O Fsulfonamide 309 0 o / CI NH 0 N-(5-chloro-2-{[(3-chloro 2 methylphenyl)sulfonyl]ami Method A NH no}phenyl)-1-benzofuran IC S= CI 1 2-sulfonamide 179 WO 2012/082633 PCT/US2011/064441 310 CI NH N-{5-chloro-2 [(isobutylsulfonyl)amino]ph Method A NH enyl}-1-benzofuran-2 sulfonamide o6
CH
3
CH
3 311 / CI NH 0 5-[({2-[(1 -benzofuran-2 F ylsulfonyl)amino]-4 NH chlorophenyl}amino)sulfon Method B I /yl]-2-chloro-4 fluorobenzoic acid OH 312 1 CIN 0N-{5-[({2-[(1 -benzofuran-2
CH
3 ylsulfonyl)amino]-4 NH chlorophenyl}amino)sulfon Method A I N yl]-4-methyl-1,3-thiazol-2 11 I yl}acetamide O N
CH
3 o 313 CI NH N-(5-chloro-2-{[(2,5 F difluorophenyl)sulfonyl]ami Method A NH no}phenyl)-1-benzofuran 2-sulfonamide F 314 0 CI NH 0N-(5-chloro-2-{[(4-chloro Cl- NH 02,5 F difluorophenyl)sulfonyl]ami Method A NH no}phenyl)-1-benzofuran o=6 %O/ C 2-sulfonamide 180 WO 2012/082633 PCT/US2011/064441 315 0 CI NH 0 N-(5-chloro-2-{[(4-chloro 3 NH ___ methylphenyl)sulfonyl]ami Method A NH no}phenyl)-l-benzofuran o=sI C 2-sulfonamide 0
OH
3 316 CI NH N-{2-[(l-benzofuran-2 ylsulfonyl)amino]-4- Method A H chlorophenyl}-1 H-1,2,4 NH N triazole-5-sulfonamide o=b o N 0 317 1 o=s Ci NH 0 3-{4-[({2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method B NH chlorophenyl}amino)sulfon O=S O yl]phenyl}propanoic acid 0 OH 318 0 methyl 3-[({2-[(1 benzofuran-2 NH CI ylsulfonyl)amino]-4 chlorophenyl}amino)sulfon Method A II s yl]-5-chlorothiophene-2 o carboxylate 0
CH
3 319 CI NH N-{2-[(1 -benzofuran-5 ylsulfonyl)amino]-5- Method A NH chlorophenyl}-1 I -benzofuran-2-sulfonamide O=S/ 0 181 WO 2012/082633 PCT/US2011/064441 320 0 o=s CI NH o<0 N-{3-[({2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method A N NH chlorophenyl}amino)sulfon IH yl]phenyl}acetamide 00 321 0 o=s CI NH 0 N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method A NH chlorophenyl}-2 = oxoindoline-5-sulfonamide 0 322 CI NH 0 N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-3,5- Method A NH NHdimethyl-1 H-pyrazole-4 s / IH sulfonamide I I -N 0 323 / C I NH N-[5-chloro-2-({[4-(2 NH methylphenoxy)phenyl]sulf Method A I onyl}amino)phenyl]-1 O= 0 benzofuran-2-sulfonamide C H 3 " 324 0 /N-{2-[(1-benzofuran-2 s copylsulfonyl)amino]-4 NH H chlorophenyl}-2-oxo-2,3- Method A __- N>= dihydro-1,3-benzoxazole CI NH O O 6-sulfonamide 0\ 325 3 N-{2-[(1-benzofuran-2 O ylsulfonyl)amino]-4 NH chlorophenyl}-2-chloro- Method C
-
N CI( -NH CI 1,3-benzothiazole-6 /s sulfonamide 0 182 WO 2012/082633 PCT/US2011/064441 326 / CI NH o 5-[({2-[(1-benzofuran-2 ylsulfonyl)amino]-4 COOH chlorophenyl}amino)sulfon Method B NH y]-2-ethoxybenzoic acid 327 0 <J) CI NH 0 3-[({2-[(1 -benzofuran-2 F ylsulfonyl)amino]-4- Method B NH chlorophenyl}amino)sulfon I yl]-4-fluorobenzoic acid COOH 328 0 CI NH N-(5-chloro-2-{[(2,6 dimethylphenyl)sulfonyl]a Method A NH mino}phenyl)-1 I -benzofuran-2-sulfonamide 329 CI NH 0 N-{2-[(1 -benzofuran-2 ylsulfonyl)amino]-4- Method A / chlorophenyl}isoquinoline o=s 5-sulfonamide N 330 CI NH aN-(5-chloro-2-{[(2 methylphenyl)sulfonyl]ami Method A no}phenyl)-1-benzofuran NH 2-sulfonamide II O=b 0 183 WO 2012/082633 PCT/US2011/064441 331 CI NH N-(5-chloro-2-{[(2,4 difluorophenyl)sulfonyl]ami Method A no}phenyl)-1-benzofuran NH 2-sulfonamide II 0F 0 332 0 o=s 332NHN-(5-chloro-2-{[(5 CINH 0 0isoxazol-3-yl-2 N' thienyl)sulfonyl]amino}phe Method A NH / nyl)-1-benzofuran-2 = sulfonamide 0 333 0 o=s CI NH 0 4-[({2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method B NH chlorophenyl}amino)sulfon I COyl]benzoic acid II /COOH 0 334 CI NH N-(5-chloro-2-{[(3,4 dimethylphenyl)sulfonyl]a Method A mino}phenyl)-1 NH benzofuran-2-sulfonamide I 3350 o=s CI NH 3-[({2-[(1-benzofuran-2 ylsulfonyl)amino]-4 COOH chlorophenyl}amino)sulfon Method B NH yl]benzoic acid o=s 336 0 336NHi N-{4-[({2-[(1-benzofuran-2 ylsulfonyl)amino]-4 NH chlorophenyl}amino)sulfon Method A O= / NH O= Nmethylphenyllacetamide
CH
3 0 184 WO 2012/082633 PCT/US2011/064441 337 0 337NHi0N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-2- Method C NH chloroquinoline-6 =S N sulfonamide u11 cl 338 0 CI NH O N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method A NH -N chlorophenyl}quinoline-3 I sulfonamide 339 0 339 N-{2-[(1-benzofuran-2 CI NH _ ylsulfonyl)amino]-4 N chlorophenyl}-5- Method A NH chloroquinoline-8 I CI sulfonamide 3400 CI NH 0 N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method A NH chlorophenyl}quinoline-6 N sulfonamide 341 CI NH N-(5-chloro-2-{[(2,4 dimethylphenyl)sulfonyl]a Method A NH mino}phenyl)-1 I -benzofuran-2-sulfonamide U=b 0 185 WO 2012/082633 PCT/US2011/064441 342 / CI NH 0 5-[({2-[(1-benzofuran-2 HO ylsulfonyl)amino]-4- Method B NH chlorophenyl}amino)sulfon I yl]-2-methoxybenzoic acid o=% 0 o CH 3 343 0 II CI NH N-(5-chloro-2-{[(2,4 dimethoxyphenyl)sulfonyl] Method A NH amino}phenyl)-1 O=S o benzofuran-2-sulfonamide 0 344 ci 0= 0 CI :) NH 0N-[2-({[3,5 bis(trifluoromethyl)phenyl]
CF
3 sulfonyl}amino)-5- Method C H chlorophenyl]-1 0= benzofuran-2-sulfonamide
CF
3 3450 7 o=b CI NH N-(5-chloro-2-{[(5-chloro Cl)::) NH C)2 CI fluorophenyl)sulfonyl]amin Method A NH o}phenyl)-1-benzofuran-2 0 U=6 sulfonamide F 346 CI NH N-(5-chloro-2-{[(2,3 dichlorophenyl)sulfonyl]am Method A NH ino}phenyl)-1-benzofuran I --- 2-sulfonamide C11 186 WO 2012/082633 PCT/US2011/064441 3470 CI NH N-(5-chloro-2-{[(2,6 F difluorophenyl)sulfonyl]ami Method A NH no}phenyl)-1 -benzofuran 2-sulfonamide 0 F 348 CI NH N-(5-chloro-2-{[(2,5 C1 dichlorophenyl)sulfonyl]am Method A NH ino}phenyl)-1-benzofuran I 2-sulfonamide CI 349 ci 0 0 N-{2-[(1-benzofuran-2 || 11 ylsulfonyl)amino]-4 O=s-NH HN chlorophenyl}-1- Method A o (phenylsulfonyl)-1 H 6NN pyrrole-3-sulfonamide 350 0 CI NH N-(5-chloro-2-{[(2,6 dichlorophenyl)sulfonyl]am Method A NH ino}phenyl)-1 -benzofuran I= 2-sulfonamide CI 351 / N-(5-chloro-2-{[(3-chloro C1NH 0 4 ci methylphenyl)sulfonyl]ami Method A NH no}phenyl)-1-benzofuran O CH3 2-sulfonamide 187 WO 2012/082633 PCT/US2011/064441 352 CI NH 0 N-[5-chloro-2-({[2 NH (methylsulfonyl)phenyl]sulf Method A onyl}amino)phenyl]-1 0 0=3=0 benzofuran-2-sulfonamide CH 0 3530 353N HN-(5-chloro-2-{[(2,5 dichloro-3 C1 thienyl)sulfonyl]amino}phe Method C NH nyl)-1-benzofuran-2 /S sulfonamide II o ci 3540 o=sj CI NH N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method A chlorophenyl}-1
H
I -N pyrazole-4-sulfonamide 0 355 0 N-{5-chloro-2-[(2,3 CI,,,N N dihydro-1 H-inden-5 ylsulfonyl)amino]phenyl}- Method A NH 1-benzofuran-2 I sulfonamide 356 o= methyl 4-[({2-[(1 CI NH benzofuran-2 ylsulfonyl)amino]-4- Method A NH O-CH 3 chlorophenyl}amino)sulfon = 1yl]benzoate 188 WO 2012/082633 PCT/US2011/064441 3570 CI NH N-(5-chloro-2-{[(2,4,5 F trifluorophenyl)sulfonyl]am Method A NH ino}phenyl)-1-benzofuran I F 2-sulfonamide F 358 CI 0NH N-(5-chloro-2-{[(3,5 dimethylphenyl)sulfonyl]a Method A NH mino}phenyl)-1 I benzofuran-2-sulfonamide 359 0 CI NH o N-(5-chloro-2-{[(4 methoxy-3 methylphenyl)sulfonyl]ami Method A H CH3 no}phenyl)-1-benzofuran o= 2-sulfonamide 0
CH
3 360 0 o=s N-{2-[(1 -benzofuran-2 CI NH 0 ylsulfonyl)amino]-4 chlorophenyl}-2-oxo- Method A NH 1,2,3,4 NH tetrahydroquinoline-6 sulfonamide o 0 0 361 o=s CI NH 0 CH 3 N-(5-chloro-2-{[(5 HN- CH 3 {[(dimethylamino)carbonyl] NH 0 amino}-2 o=s ethoxyphenyl)sulfonyl]ami Method A 0 nolphenyl)-1 -benzofuran 0) 2-sulfonamide
CH
3 189 WO 2012/082633 PCT/US2011/064441 362 0 o=s CI NH O N-(5-chloro-2-{[(2-ethoxy izk N HN-CH, 5 NH HN {[(methylamino)carbonyl]a o=s mino}phenyl)sulfonyl]amin 0 olphenyl)-1 -benzofuran-2 sulfonamide
CH
3 363 CI NH 0 N-(2-[(4 0 acetylphenyl)sulfonyl]amin Method A o}-5-chlorophenyl)-1 NH benzofuran-2-sulfonamide 0 364 0I o=s 364N methyl 3-[({2-[(1 CI NH benzofuran-2 0 O% ylsulfonyl)amino]-4- Method A NH chlorophenyl}amino)sulfon I yl]benzoate 0 365 0 CI NH N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-2-oxo-2,3- Method A H dihydro-1,3-benzothiazole O=S NH 6-sulfonamide os o 366 0 CI NH 0 N-{5-[({2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}amino)sulfon Method A NH Nyl]-1,3-thiazol-2 = 0 yl}acetamide H 190 WO 2012/082633 PCT/US2011/064441 367 / CI NH O N-(5-chloro-2-{[(3-chloro 4 methoxyphenyl)sulfonyl]a Method A H mino}phenyl)-1 S= o benzofuran-2-sulfonamide o CH 3 CI 368 cl 0 NH 0N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method A 0 NH chlorophenyl}-2-oxo-2H chromene-6-sulfonamide 0 0 369 CI NH N-(5-chloro-2-{[(5-chloro Cl-_NH 02,4 F difluorophenyl)sulfonyl]ami Method A NH no}phenyl)-1-benzofuran O=S / F 2-sulfonamide CI 370 0 CI NHO N-{5-[({2-[(1 -benzofuran-2 ylsulfonyl)amino]-4 NH CH 3 chlorophenyl}amino)sulfon Method A o=, Io yl]-2 o methoxyphenyl}acetamide NH CH3 0 00 371 N-{2-[(1 -benzofuran-2 CI NH ylsulfonyl)amino]-4 chlorophenyl}-6- Method A NH N _ morpholin-4-ylpyridine-3 O=S / N O sulfonamide N 191 WO 2012/082633 PCT/US2011/064441 372 0 ci methyl 5-[({2-[(1 benzofuran-2 NH ylsulfonyl)amino]-4- Method C chlorophenyl}amino)sulfon =13 K yl]-4-methoxythiophene-3 0 CH 3 carboxylate 373 OH 3 CI NH 0 N-{5-chloro-2-[(3 furylsulfonyl)amino]phenyl Method C }-1 -benzofuran-2 NH sulfonamide U= 0 NH 0 N-{5-chloro-2-[({4-[(6 methylpyrazin-2 NH yl)oxy]phenyl}sulfonyl)ami Method A O=S a no]phenyl}-1 -benzofuran S / 2-sulfonamide 375 CI NH 0 N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-1 -methyl- Method C NH 1 H-pyrazole-5 o=6 sulfonamide u/N- N 0 376 0= N-{2-[(1 -benzofuran-2 CI NH 0 ylsulfonyl)amino]-4 chlorophenyl}-6- Method C NH phenylpyridine-3 o=s L / sulfonamide 377 < 3=0 N-[5-chloro-2-({[4-(1 CI NH methyl-1 H-pyrazol-3 yl)phenyl]sulfonyl}amino)p Method A NH N henyl]-1-benzofuran-2 o=S sulfonamide 192 WO 2012/082633 PCT/US2011/064441 3780 378 N-{2-[(1-benzofuran-2 CI NH ylsulfonyl)amino]-4 chlorophenyl}-6- Method C NH N chloroimidazo[2,1 I b][1,3]thiazole-5 II N sulfonamide 0 CI 379 0 379N 0 N-{5-chloro-2-[({3-[(6 CI NN methylpyrazin-2 NH o yl)oxy]phenyl}sulfonyl)ami Method A NH - N no]phenyl}-1 -benzofuran 0s /2-sulfonamide 380 / 30 NH methyl 5-[({2-[(1 CIa NH 0benzofuran-2 o ylsulfonyl)amino]-4- Method C NH O/ chlorophenyl}amino)sulfon o=S yl]-2-furoate 0 381 / CI NH 0 O N-[5-chloro-2-({[3-(5 methyl- 1,2,4-oxadiazol-3 NH -yl)phenyl]sulfonyl}amino)p Method A o=s henyl]-1 -benzofuran-2 u /sulfonamide N NO 0 382 I o=s CI NH 0 N-(5-chloro-2-{[(3 pyrimidin-2 NH ylphenyl)sulfonyl]amino}ph Method A o=s enyl)-1 -benzofuran-2 11 /sulfonamide N N 193 WO 2012/082633 PCT/US2011/064441 0 383 11/ 3I 83 1-acetyl-N-{2-[(1 CI NH benzofuran-2 o ylsulfonyl)amino]-4- Method C H chlorophenyl}indoline-5 1-1 N sulfonamide 0 384 CI NH 0 ethyl 3-[({2-[(1 benzofuran-2 NH N ylsulfonyl)amino]-4- Method A = chlorophenyl}amino)sulfon yl]isonicotinate 0 0 385 0 385 N-(5-chloro-2-{[(5-methyl CINH0 1-benzothien-2 yl)sulfonyl]amino}phenyl)- Method A NH 1-benzofuran-2 = sulfonamide 0 386 / CINH N-[5-chloro-2-({[3-(1 methyl-1 H-pyrazol-5 NH yl)phenyl]sulfonyl}amino)p Method A o= henyl]-1-benzofuran-2 o ,CH 3 sulfonamide N 387 0 o=s5 CI NH 0 N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method A NH chlorophenyl}chromane-6 sulfonamide 194 WO 2012/082633 PCT/US2011/064441 388 0 CI NH o N-(5-chloro-2-{[(2-chloro 4 NH cyanophenyl)sulfonyl]amin Method A I H o}phenyl)-l-benzofuran-2 o=; N sulfonamide cl 0 389y o= ethyl 5-[({2-[(l CI NH 0 benzofuran-2 0 ylsulfonyl)amino]-4- Method C NH 0 -'l'CH 3 chlorophenyl}amino)sulfon o=s |yl]-3-furoate o 0 390 / CI NH 0 methyl 3-[({2-[(l 0 CH 3 benzofuran-2 0 ylsulfonyl)amino]-4- Method A H chlorophenyl}amino)sulfon yl]-4-methoxybenzoate
CH
3 0 391 o=> / N-(5-chloro-2-{[(4 CI NH O pyrimidin-2 ylphenyl)sulfonyl]amino}ph Method A NH N enyl)-1-benZofuran-2 sulfonamide 392 o= N-[5-chloro-2-({[3-(5 CI NH methyl- 1,3,4-oxadiazol-2 yl)phenyl]sulfonyl}amino)p Method C NH O henyl]-1-benzofuran-2 O=S I sulfonamide 393 0 11 393 N > N-[5-chloro-2-({[2-chloro cIa NH -4 cl (trifluoromethyl)phenyl]sulf Method A NH F onyl}amino)phenyl]-1 O F benzofuran-2-sulfonamide o F 195 WO 2012/082633 PCT/US2011/064441 3940 Ii N-(5-chloro-2-{[(2,5 CI a NH dimethyl-3
CH
3 furyl)sulfonyl]amino}pheny Method A NH I)-1 -benzofuran-2 = 0 sulfonamide || o
CH
3 3950 39 N methyl 5-[({2-[(l CI NH benzofuran-2 ylsulfonyl)amino]-4- Method A NH chlorophenyl}amino)sulfon s yl]-l -methyl-1 H-pyrrole-2 u N O carboxylate / 1CH 3
CH
3 0 0 396 Ci/N-[5-chloro-2-({[4-(3,5 cI NH dimethyl-1 H-pyrazol-1 NH ; CH3 yl)phenyl]sulfonyl}amino)p Method A O N henyl]-1-benzofuran-2 III N /sulfonamide 0
CH
3 3970 CI NH N-(5-chloro-2-{[(4-chloro 2-fluoro-5
CH
3 methylphenyl)sulfonyl]ami Method A NH no}phenyl)-1-benzofuran o=s ci 2-sulfonamide 3980 9 CN-{2-[(1-benzofuran-2 CN 0ylsulfonyl)amino]-4 chlorophenyl}-1 -methyl- Method A NH 1 H-pyrazole-3 = N sulfonamide 196 WO 2012/082633 PCT/US2011/064441 399 0 CI NH O N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4
CH
3 chlorophenyl}-3,5- Method A / N dimethyl-1-phenyl-1H 0= pyrazole-4-sulfonamide
CH
3 400 0 ~ /N-{2-[(1-benzofuran-2 s "CPylsulfonyl)amino]-4 oS NH chlorophenyl}-4-methyl- Method A _ 3,4-dihydro-2H-1,4 CI NH benzoxazine-6 S~a N sulfonamide O
CH
3 401 0I 401N N-{2-[(1-benzofuran-2 CI N 0ylsulfonyl)amino]-4 chlorophenyl}-3,4-dihydro- Method A NH 2H-1,5-benzodioxepine-7 = sulfonamide 402 0 C NH N-[5-chloro-2-({[3-(1 methyl-1 H-pyrazol-3 H /yl)phenyl]sulfonyl}amino)p Method A o henyl]-1-benzofuran-2 0 sulfonamide N N, CH3 403 Cl NH 0 N-{5-chloro-2-[(2,3 dihydro-1-benzofuran-5 ylsulfonyl)amino]phenyl}- Method A NH 1-benzofuran-2 O=b sulfonamide 1197 197 WO 2012/082633 PCT/US2011/064441 404 0 o=s CI NH 0 N-[5-chloro-2-({[4 (pyrrolidin-1 NH 0 ylsulfonyl)phenyl]sulfonyl} Method A I - 1_ amino)phenyl]-1 =O benzofuran-2-sulfonamide 11 o 405 CI NH N-(5-chloro-2-{[(5-methyl 2 furyl)sulfonyl]amino}pheny Method A NH l)-1 -benzofuran-2 I= sulfonamide O
CH
3 4060 NH60CI N-(5-chloro-2-{[(5-methyl CIaH0 0 2 thienyl)sulfonyl]amino}phe Method A NH V CH 3 nyl)-1-benzofuran-2 = sulfonamide 0 407 CI NH N-{2-[(1-benzofuran-2 C I-_ NH -N 0ylsulfonyl)am ino]-4- M method A I ~ N "N~ chlorophenyl}-1 -methyl
N
H 1 H-indole-7-sulfonamide U=6 11 0 408 CI NH N-{5-chloro-2-[(2,3 dihydro-1-benzofuran-7 NH ylsulfonyl)amino]phenyl}- Method A 1H 1 -benzofuran-2 = sulfonamide 0 198 WO 2012/082633 PCT/US2011/064441 409 1 NH 0N-{2-[(l -benzofuran-2 ylsulfonyl)amino]-4 0=S=0 chlorophenyl}-2,2- Method A dimethylchromane-6 sulfonamide 0 410 0 1 o=s N-[5-chloro-2-({[4-(2 CI NH methyl-1,3-thiazol-4 yl)phenyl]sulfonyl}amino)p Method A NH N CH 3 henyl]-1-benzofuran-2 0S sulfonamide 0 411 0 o=s CI NH 0 N-{2-[(1-benzofuran-2
CH
3 ylsulfonyl)amino]-4 NH chlorophenyl}-4-methyl-2- Method A / Nphenyl-1,3-thiazole-5 11 sulfonamide 412 0 412 I N-{2-[(1 -benzofuran-2 CI NH 0 ylsulfonyl)amino]-4 chlorophenyl}-6- Method A NH- phenoxypyridine-3 o= / 0 sulfonamide 0 N 413 0 C41NH 0 methyl 5-[({2-[(1 benzofuran-2 0 C ylsulfonyl)amino]-4- Method A NH /CH3 chlorophenyl}amino)sulfon / yl]-2-methyl-3-furoate o 0
CH
3 199 WO 2012/082633 PCT/US2011/064441 4140 C4 NH N-[5-chloro-2-({[4 (phenoxymethyl)phenyl]su Method A NH Ifonyl}amino)phenyl]-1 o= benzofuran-2-sulfonamide 0 415 0 o=s CI NH 5-[({2-[(1 -benzofuran-2 NH __ ylsulfonyl)amino]-4- Method B NH chlorophenyl}amino)sulfon O= OH yl]-2-hydroxybenzoic acid OH 416 0I 416NHN-(5-chloro-2-{[(5-pyridin CIa NH 0 2.y|..2.. N thienyl)sulfonyl]amino}phe Method A NH nyl)-1-benzofuran-2 o= sulfonamide 417 0 o=s CI NH 0 N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-2-methyl- Method A N H 1,3-benzothiazole-6 = / N sulfonamide Slk 4180 418 N-{2-[(1-benzofuran-2 CI NH 0 ylsulfonyl)amino]-4 chlorophenyl}-4-methyl- Method A NH 0- 3,4-dihydro-2H-pyrido[3,2 b][1,4]oxazine-7 U= N sulfonamide 0 N 200 WO 2012/082633 PCT/US2011/064441 419 0 N-{2-[(1 -benzofuran-2 ylsulfonyl)amino]-4- Method A NH chlorophenyl}-1 -methyl = 1 1 H-indole-4-sulfonamide N 420 0 CI NH N-(5-chloro-2-{[(5-phenyl CII NH C.. Cl-,,a NH 02 thienyl)sulfonyl]amino}phe Method A NH snyl)-1-benzofuran-2 = sulfonamide 4210 42 / N-{2-[(1 -benzofuran-2 CI NH ylsulfonyl)amino]-4 N chlorophenyl}-3-oxo-3,4- Method A HN dihydro-2H-1,4 IH benzoxazine-6 o= / o sulfonamide 422 0 422NHci N-(5-chloro-2-{[(4 / NH phenoxyphenyl)sulfonyl]a Method A a NH mino}phenyl)-1 i - benzofuran-2-sulfonamide 0=S 11 0 423 0 CI NH 0 N-{2-[(1-benzothien-2 ylsulfonyl)amino]-5- Method A chlorophenyl}-1 NH benzofuran-2-sulfonamide U=b 0 424 y1</ ,; o=S N-(5-chloro-2-{[(4' ci NH fluorobiphenyl-4 yl)sulfonyl]amino}phenyl)- Method A N 1-benzofuran-2 O=S F sulfonamide 201 WO 2012/082633 PCT/US2011/064441 425 0 CI NH o N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-1,3,5- Method A NH trimethyl-1 H-pyrazole-4 O=b I sulfonamide o N 426 CI NH 0 N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4
CH
3 chlorophenyl}-5-chloro- Method A NH 1,3-dimethyl-1 H-pyrazole O=I I 4-sulfonamide IIN o
"CH
3 CI 427 / 427NHci 2-{4-[({2-[(1-benzofuran-2 ylsulfonyl)amino]-4- Method A chlorophenyl}amino)sulfon O
ONH
2 yl]phenoxy}acetamide 0 428 c0 5-[({2-[(1 -benzofuran-2 NH _ylsulfonyl)amino]-4- Method B H chlorophenyl}amino)sulfon O=S CH 3 yl]-2-methylbenzoic acid OH 429 0 CI NH 0O 3-[({2-[(1 -benzofuran-2 NH CH 3 ylsulfonyl)amino]-4- Method B I chlorophenyl}amino)sulfon O=b yl] -4-m ethyl benzoic acid 0 HO 202 WO 2012/082633 PCT/US2011/064441 430 0 CI N5-[({2-[(1 -benzofuran-2 CH ylsulfonyl)amino]-4 NH chlorophenyl}amino)sulfon Method B O C/ yl]-2,4-dichlorobenzoic acid 0 0 HO 431 0 CI NH N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-5,6- Method C NH -N dichloropyridine-3 o=/ ci sulfonamide CI 432 1 N-(5-chloro-2-{[(2,4 NH dichloro-5 I methylphenyl)sulfonyl]ami Method A O=s=0 no}phenyl)-1 -benzofuran C1 2-sulfonamide CI 433 0 CI NH 0 N-(5-chloro-2-{[(3-fluoro-4 F methoxyphenyl)sulfonyl]a Method A FH mino}phenyl)-1 NH
CH
3 benzofuran-2-sulfonamide 0=S0 434 0 o=S CI NH - N-(5-chloro-2-{[(4-chloro Cl~a NH 02 fluorophenyl)sulfonyl]amin Method A NH o}phenyl)-1-benzofuran-2 o=s C1 sulfonamide F 203 WO 2012/082633 PCT/US2011/064441 4350 CI NH 0 NH N-[5-chloro-2-({[4-(1
H
pyrazol-1 O=S=0 yl)phenyl]sulfonyl}amino)p Method A henyl]-1 -benzofuran-2 sulfonamide N 436 CINH 0N-(5-chloro-2-{[(2,5 dimethyl-3 NH thienyl)sulfonyl]amino}phe Method A o=s=o nyl)-1 -benzofuran-2 sulfonamide S 437 CI NH 0 NH N-[5-chloro-2-({[4 o=s=o (difluoromethoxy)phenyl]s Method A ulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide 0 F F 204 WO 2012/082633 PCT/US2011/064441 438 N-(5-chloro-2-{[(2-fluoro-4 NH methylphenyl)sulfonyl]ami 0=3=o no}phenyl)-1-benzofuran 2-sulfonamide F 439 0 ,NH 0N -[5-ch lo ro -2 -({[4 -fluo ro -3 NH (trifluoromethyl)phenyl]sulf Method A o=s=o onyl}amino)phenyl]-1 benzofuran-2-sulfonamide
F
3 C F 440 o=b CI_ NH N-(5-chloro-2-{[(3-chloro 2 NH fluorophenyl)sulfonyl]amin Method C o=s=o o}phenyl)-1 -benzofuran-2 F sulfonamide CI 441 CI NH 0 N-(5-chloro-2-{[(3-cyano NH 4 N fluorophenyl)sulfonyl]amin Method A O=s=0 o}phenyl)-1 -benzofuran-2 sulfonamide CN F 205 WO 2012/082633 PCT/US2011/064441 442 CI NH0 N-(5-chloro-2-{[(5-chloro NH 2 I naphthyl)sulfonyl]amino}p Method A OSO0 henyl)-1 -benzofuran-2 sulfonamide CI 4430 U=s CI NH l-_ a NH N-{2-[(biphenyl-3 NH ylsulfonyl)amino]-5- Method A 0=S=0 chlorophenyl}-1 benzofuran-2-sulfonamide 444 CI NH N-{2-[(1 -benzofuran-2 ylsulfonyl)amino]-4 NH chlorophenyl}-2- Method A I chloropyridine-3 sulfonamide CI 445 CI NH 0 N-{2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4- Method A chlorophenyl}pyridine-3 0=S=0 sulfonamide N206 206 WO 2012/082633 PCT/US2011/064441 446 0 o=s CI NH N-{2-[(1-benzofuran-2 ylsulfonyl)amino]-4 chlorophenyl}-2,3-dihydro- Method A NH 1,4-benzodioxine-6 o=s o sulfonamide u~0j 447 0 4 N N-(5-chloro-2-{[(5 CIN isoxazol-5-yl-2 thienyl)sulfonyl]amino}phe Method A NH s / nyl)-1-benzofuran-2 o=~ sulfonamide 0 448 0 CI NH 0O N-(5-chloro-2-{[(3,5 NH dichloro-4 I hydroxyphenyl)sulfonyl]am Method A O=s=0 ino}phenyl)-1 -benzofuran 2-sulfonamide CI CI OH 449 CI NH O 5-[({2-[(1 -benzofuran-2 "a NH ylsulfonyl)amino]-4 o=s=o chlorophenyl}amino)sulfon yl]-2-fluorobenzoic acid COOH F 207 WO 2012/082633 PCT/US2011/064441 450 U=b CI NH N-{2-[(1 -benzofuran-2 ylsulfonyl)amino]-4 NH chlorophenyl}-1,2- Method A o=s=o dimethyl-1 H-imidazole-4 sulfonamide N
N
451 0 NNH N-(2-{[(4-bromo-3 NH methylphenyl)sulfonyl]ami o=s=o no}-5-chlorophenyl)-1 benzofuran-2-sulfonamide Br 452 CI NH 0 N-(5-chloro-2-{[(2-fluoro-5 NH methylphenyl)sulfonyl]ami Method A no}phenyl)-1-benzofuran O=s=0 2-sulfonamide F 208 WO 2012/082633 PCT/US2011/064441 453 CI NH NH N N-(5-chloro-2-{[(4' 0=S=o chlorobiphenyl-4 yl)sulfonyl]amino}phenyl)- Method A 1-benzofuran-2 sulfonamide CI CI NH 0 NH N-[5-chloro-2-({[3-(2 methylpyrimidin-4 0=s=O yl)phenyl]sulfonyl}amino)p Method A henyl]-1 -benzofuran-2 sulfonamide N N 4550 o=b CI NH 0 NH 0N-[5-chloro-2-({[5-(1,3 NH oxazol-5-yl)-2 o=s=o thienyl]sulfonyl}amino)phe Method A nyl]-1 -benzofuran-2 s sulfonamide N O 209 WO 2012/082633 PCT/US2011/064441 456 CI NH 0 N-[5-chloro-2-({[4-chloro NH 3 | (trifluoromethyl)phenyl]sulf Method A O=S=0 onyl}amino)phenyl]-1 benzofuran-2-sulfonamide
CF
3 CI 4570 CI NH 0 N-{2-[(biphenyl-2 NH ylsulfonyl)amino]-5- Method A chlorophenyl}-1 0=S=O benzofuran-2-sulfonamide 458 0 U=b CI NH NH 0N-{2-[(l -benzofuran-2 NH ylsulfonyl)amino]-4 o=s=o chlorophenyl}-2-oxo- Method A 2,3,4,5-tetrahydro-1 H-1 benzazepine-7 sulfonamide HN 0 459 CI NH 0 N-(5-chloro-2-{[(3-chloro NH 4~ I cyanophenyl)sulfonyl]amin Method A O=s=o o}phenyl)-1 -benzofuran-2 sulfonamide CI CN 210 WO 2012/082633 PCT/US2011/064441 460 CI NH 3-[({2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4- Method B I chlorophenyl}amino)sulfon 0=s=O yl]-4-chlorobenzoic acid CI HOOC 461 0 CNH 0 N-(2-{[(3 NH acetylphenyl)sulfonyl]amin o=s=o o}-5-chlorophenyl)-1 benzofuran-2-sulfonamide 462 0 CI NH0 N-{2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4 chlorophenyl}-6- Method C O=S=o chloropyridine-3 sulfonamide CI 463 CINH 0N-(5-chloro-2-{[(5-chloro 2 NH methylphenyl)sulfonyl]ami Method A o=s=o no}phenyl)-1 -benzofuran 2-sulfonamide 211 WO 2012/082633 PCT/US2011/064441 464 CI NH 0 NH 05-[({2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4 o=s=o chlorophenyl}amino)sulfon yl]-2-chlorobenzoic acid HOOC CI 465 CINH 0 N-{3-[({2-[(1 -benzofuran-2 ylsulfonyl)amino]-4 NH chlorophenyl}amino)sulfon Method A o=6=0 yl]-4 methylphenyl}acetamide H N 466 0 U=b CI ~ NH H N-(5-chloro-2-{[(4 =S=0 cyclohexylphenyl)sulfonyl] Method A amino}phenyl)-1 benzofuran-2-sulfonamide 212 WO 2012/082633 PCT/US2011/064441 467 U=s CI NH N-{5-chloro-2-[(5,6,7,8 NH tetrahydronaphthalen-2 1 ylsulfonyl)amino]phenyl}- Method A U~b~ 1 -benzofuran-2 sulfonamide 468 CI NH 0 3-[({2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4- Method B I chlorophenyl}amino)sulfon 0=S=0 yl]-4-methoxybenzoic acid OMe HOOC 469 0 NH 0N-{2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4 o=s=o chlorophenyl}-2,3-dioxo- Method C 1,2,3,4 tetrahydroquinoxaline-6 sulfonamide NH HN 0 213 WO 2012/082633 PCT/US2011/064441 470 CI NH 0 N-{2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4 chlorophenyl}-6- Method A O=S=0 methoxypyridine-3 sulfonamide N OMe 471 CI NH 4-acetyl-N-{2-[(1 benzofuran-2 IH ylsulfonyl)amino]-4- Method A 0=S=0 chlorophenyl}-3,4-dihydro 2H-1 ,4-benzoxazine-6 0 sulfonamide 0 472 U=s CI NH N-[5-chloro-2-({[5 NH (dimethylamino)-1 I naphthyl]sulfonyl}amino)p Method A OSO0 henyl]-1 -benzofuran-2 sulfonamide N 214 WO 2012/082633 PCT/US2011/064441 473 C1 NH 0 NH N-{4-[({2-[(1 -benzofuran-2 ylsulfonyl)amino]-4 0=S=0 chlorophenyl}amino)sulfon Method A yl]-2 chlorophenyl}acetamide 0 NH 4740 =bs C1 NH NH N-[5-chloro-2-({[4-(pyridin 1 3 O=S=o yloxy)phenyl]sulfonyl}amin Method C o)phenyl]-1 -benzofuran-2 sulfonamide N 475 0 N-(2-{[(5-tert-butyl-2 NH methylphenyl)sulfonyl]ami Method A no}-5-chlorophenyl)-1 o=s=o benzofuran-2-sulfonamide t-Bu 215 WO 2012/082633 PCT/US2011/064441 476 CI NH 0 N-1 -- {2-[(1 -benzofuran-2 NH ylsulfonyl)amino]-4 chlorophenyl}-4- Method A O=S=0 chlorobenzene-1,3 disulfonamide
SO
2
NH
2 CI 477 CI NH NH N-[5-chloro-2-({[4-(2 0=6=0 chlorophenoxy)phenyl]sulf Method A onyl}amino)phenyl]-1 benzofuran-2-sulfonamide CI 0 1 478 CI NH NH N-[5-chloro-2-({[4-(pyridin 1 2 =S= yloxy)phenyl]sulfonyl}amin Method C o)phenyl]-1 -benzofuran-2 sulfonamide O N 216 WO 2012/082633 PCT/US2011/064441 4790 CI NH 0 NH N-{4-[({2-[(1-benzofuran-2 O=s=o ylsulfonyl)amino]-4- Method C chlorophenyl}amino)sulfon yl]benzyl}acetamide HN COMe 480 0 methyl 5-[({2-[(1 NH benzofuran-2 ylsulfonyl)amino]-4- Method A O=s=0 chlorophenyl}amino)sulfon yl]-2-methyl benzoate COOMe 481 CI NH 0O methyl 2-[({2-[(1 benzofuran-2 NH ylsulfonyl)amino]-4- Method C O=s=O chlorophenyl}amino)sulfon MeOOC yl]-4-methoxybenzoate OMe 482 CINH methyl 3-[({2-[(1 benzofuran-2 NH ylsulfonyl)amino]-4- Method A O=s=o chlorophenyl}amino)sulfon yl]-2-methyl benzoate MeOOC 217 WO 2012/082633 PCT/US2011/064441 483 0 CII 0N-{2-[(1 -benzofuran-2 ylsulfonyl)amino]-4 NH chlorophenyl}-3- Method A I methylquinoline-8 sulfonamide N 484 0 U=s CI NH 0 NH N-[5-chloro-2-({[6 (dimethylamino)-2 naphthyl]sulfonyl}amino)p Method A henyl]-1 -benzofuran-2 sulfonamide N 485 0 NH S N-[2-({[4-chloro-3 NH (trifluoromethyl)phenyl]sulf Method A o=s=o onyl}amino)phenyl]thiophe ne-2-sulfonamide
CF
3 CI 486 / CI NH N-{4,5-dichloro-2 CI NH [(phenylsulfonyl)amino]ph Method A enyl}thiophene-2 O== sulfonamide 218 WO 2012/082633 PCT/US2011/064441 487 / CI NH S CI NH N-{4-[({4,5-dichloro-2-[(2 0=s=o thienylsulfonyl)amino]phen Method A yl}amino)sulfonyl]phenyl}a cetamide HN 0 488 / CI NHS N-[5-chloro-2-({[4-chloro 3 NH (trifluoromethyl)phenyl]sulf Method A O=S=O onyl}amino)-4 methylphenyl]thiophene-2 sulfonamide
CF
3 CI 489 0 / NH N N-[2-({[4-chloro-3 NH (trifluoromethyl)phenyl]sulf onyl}amino)phenyl]-1- Method A O=s=o methyl-1 H-imidazole-4 sulfonamide
CF
3 CI 219 WO 2012/082633 PCT/US2011/064441 490 0 O=S CI NH N N-[5-chloro-2-({[4-chloro 3 NH (trifluoromethyl)phenyl]sulf Method A 0=S=0 onyl}amino)-4 methylphenyl]pyridine-3 sulfonamide
CF
3 CI 491 0 1NH
NH
2 a NH aminophenyl)sulfonyl]amin C1 N o}-5-chlorophenyl)-4- Method A o=s=o chloro-3 (trifl uoromethyl)benzenesu Ifonamide
CF
3 CI 492 0 11N O=S CI NH 5-chloro-N-[5-chloro-2 c1 ({[4-chloro-3 NH (trifluoromethyl)phenyl]sulf N onyl}amino)-4- Method A o=s=o methylphenyl]-1,3 dimethyl-1 H-pyrazole-4 sulfonamide
CF
3 CI 220 WO 2012/082633 PCT/US2011/064441 493 0 II O=S CI NH N-[5-chloro-2-({[4-chloro 3 NH (trifluoromethyl)phenyl]sulf N onyl}amino)-4- Method A o=s=o methylphenyl]-1,3,5 trimethyl-1 H-pyrazole-4 sulfonamide
CF
3 CI 4940 O=S CI NH N-[5-chloro-2-({[4-chloro 3 NH (trifluoromethyl)phenyl]sulf onyl}amino)-4- Method A 0=6=U methylphenyl]-1 -methyl 1 H-pyrazole-4 sulfonamide
CF
3 495 0 N O=S I N CI NH N-[5-chloro-2-({[4-chloro 3 NH (trifluoromethyl)phenyl]sulf onyl}amino)-4- Method A 0=6=U methylphenyl]-1 -methyl 1 H-imidazole-4 sulfonamide
CF
3 CI 221 WO 2012/082633 PCT/US2011/064441 496 0 CI NH 4-chloro-N-{4-chloro-5 methyl-2 NH [(phenylsulfonyl)amino]ph Method A O=s=o enyl}-3 (trifl uoromethyl)benzenesu Ifonamide
CF
3 CI 497 0 NH 4-chloro-N-{5-chloro-2 CI NH [(phenylsulfonyl)amino]ph II enyl}-3- Method A triflel uoromethyl)benzenesu Ifonamide
CF
3 CI 498 0 O=S CI NH NH N-[4,5-dichloro-2-({[4-(1 H CI pyrazol-1 0=S=0 yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide 2N 222 WO 2012/082633 PCT/US2011/064441 499 0 N-[4-chloro-2-({[4-chloro cl )::) NH 1 (trifluoromethyl)phenyl]sulf Method A O=S=0 onyl}amino)phenyl]thiophe ne-2-sulfonamide
CF
3 CI 500 0 O=S 1 0 0 C1 NH s c1 NH N-[4,5-dichloro-2-({[4-(2 o=s=o methyl-1,3-thiazol-4 yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N 501 0 O=S CI NH s C1 NH N-[4,5-dichloro-2-({[4-(1,3 oxazol-5 O=s=o yl)phenyl]sulfonyl}amino)p Method A henyl]thiophene-2 sulfonamide N 223 WO 2012/082633 PCT/US2011/064441 502 0 O=Sel II NH - CI NH S methyl 5-[({4,5-dichloro-2 C1 NH [(2 _ thienylsulfonyl)amino]phen Method A OS=O yl}amino)sulfonyl]-2 (methylamino)benzoate COOMe HN 503 0 C11 o- 5-[({4,5-dichloro-2-[(2 C1 NH thienylsulfonyl)amino]phen yljamino)sulfonyl]-2- Method A 0=S=0(methylamino)benzoic acid COOH HN 504 0 O= CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method A 0=S=0 yl}-l -methyl-1 H-indole-5 sulfonamide N 224 WO 2012/082633 PCT/US2011/064441 505 0 O=S CI NH S CI NH N-{4,5-dichloro-2-[(2 I thienylsulfonyl)amino]phen Method A 0=S=0 yl}-2-oxoindoline-5 sulfonamide HN 0 506 0 O=S 1-/1 CNH N-{4,5-dichloro-2-[(2 CI NH thienylsulfonyl)amino]phen o=s=o yl}-1-methyl-2,3- Method A dioxoindoline-5 sulfonamide 0 N 0 507 0 1-0 CI NH S CINH N-{4,5-dichloro-2-[(2 CI thienylsulfonyl)amino]phen 0=6=O yl}-1 -methyl-2-oxoindoline- Method A 5-sulfonamide N Biological Data HEK-Gqi5 cells stably expressing CCR2 were cultured in (DMEM high glucose, 10% FBS, 1% PSA, 400 ptg/ml geneticin and 50 ptg/ml hygromycin. Appropriate positive 5 control chemokines (MCP-1, MIP1A or RANTES) was used as the positive control agonist for screening compound-induced calcium activity assayed on the 225 WO 2012/082633 PCT/US2011/064441 FLIPRTetra. The drug plates were prepared in 384-well microplates using the EP3 and the MultiPROBE robotic liquid handling systems. Compounds were synthesized and tested for CCR2 activity. Table 2 shows activity for CCR2 receptor (IC50) nM 5 Table 2 CCR2 IC 5 o CCR2 % Compound Name (nM) Antagonism 5-chloro-N-{4,5-dichloro-2-[(2 thienylsulfonyl)aminolphenyl}thiophene-2-sulfonamide 263 89 6-chloro-N-{4,5-dichloro-2-[(2 thienylsulfonyl)aminolphenyl}pyridine-3-sulfonamide 281 100 methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyllthiophene-2-carboxylate 246 96 N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-4,5 dichlorophenyl)thiophene-2-sulfonamide 471 91 N-(4,5-dichloro-2-{[(2,4 difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 451 89 N-(4,5-dichloro-2-{[(2 fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 402 67 N-(4,5-dichloro-2-{[(3,4 dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 394 79 N-(4,5-dichloro-2-{[(3,5-dichloro-2 hydroxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 482 82 N-(4,5-dichloro-2-{[(3-chloro-2 fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 217 96 N-(4,5-dichloro-2-{[(3 chlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 391 90 N-(4,5-dichloro-2-{[(4-chloro-2 fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 361 94 N-(4,5-dichloro-2-{[(4 fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide 441 91 226 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(2, 6 dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide 478 89 N-(5-chloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl) 1 -benzofuran-2-sulfonamide 153 99 N-(5-chloro-2-{[(5-methyl-2-thienyl)sulfonyl]amino}phenyl) 1 -benzofuran-2-sulfonamide 339 96 N-[3-({[4-chloro-3 (trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2 yllthiophene-2-sulfonamide 349 85 N-[4,5-dichloro-2-({[3 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide 306 88 N-[4,5-dichloro-2-({[4-fluoro-3 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide 432 89 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl} 1-methyl-1 H-pyrazole-3-sulfonamide 185 96 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl} 1-methyl-1 H-imidazole-4-sulfonamide 423 110 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl} 3,5-dimethyl-1 H-pyrazole-4-sulfonamide 183 108 N-{2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl} 5-chloro-1,3-dimethyl-1 H-pyrazole-4-sulfonamide 294 80 227 WO 2012/082633 PCT/US2O1 1/064441 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl-1 benzofuran-2-sulfonamide 96 100 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl-1 benzothiophene-2-sulfonamide 494 94 N-{4,5-dioh Ioro-2-[(2-thienylsulfonyl)amino]phenyl}-5 methylfuran-2-sulfonamide 311 95 N-{4-chloro-2-[(2-th ienylsulfonyl)amino] phenyl}- 1 benzofuran-2-sulfonamide 145 90 N-{5-chloro-2-[(2-th ienylsulfonyl)amino] phenyl}- 1 benzofuran-2-sulfonamide 20 86 228

权利要求:
Claims (14)
[1] 1. A compound having Formula I, its enantiomers, diastereoisomers, hydrates, solvates, crystal forms and individual isomers, tautomers or a pharmaceutically acceptable salt thereof, R 6 o=s=o R 1 5 N R 3 R1 R14 R2 R N IN R17T Ne o=s=o 5 Formula I wherein: R 1 is H or substituted or unsubstituted C1.6 alkyl; 10 R 2 is H or substituted or unsubstituted C1.6 alkyl; R 3 is N or C-R ; R 4 is N or C-R ; R 5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 15 cycloalkenyl or is substituted or unsubstituted C610 aryl; R 6 is 2-benzofuran, 2 -thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 methylphenyl, or 4-chloro-3-trifluoromethylphenyl; R 15 is N or C-R16; R 17 is N or C-R18 20 R 7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0 R 11 or hydroxyl; R 8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1.3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13 R 14 or hydroxyl; R 16 is H, substituted or unsubstituted C1-6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 25 alkenyl, C 2-6 alkynyl, C(O)R 1 9 , NR 20 R 21 or hydroxyl; R 18 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1.3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 22 , NR 23 R 24 or hydroxyl; 229 WO 2012/082633 PCT/US2011/064441 R 9 is H or substituted or unsubstituted C1-6 alkyl; R 10 is H or substituted or unsubstituted C1.6 alkyl; R" is H or substituted or unsubstituted C1.6 alkyl; R 12 is H or substituted or unsubstituted C1.6 alkyl 5 R1 3 is H or substituted or unsubstituted C1.6 alkyl; R 1 4 is H or substituted or unsubstituted C1.6 alkyl; R 1 9 is H or substituted or unsubstituted C1.6 alkyl; R 20 is H or substituted or unsubstituted C1.6 alkyl; R 2 1 is H or substituted or unsubstituted C1.6 alkyl; 10 R 22 is H or substituted or unsubstituted C1.6 alkyl; R 23 is H or substituted or unsubstituted C1.6 alkyl; R 24 is H or substituted or unsubstituted C1.6 alkyl; and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 15 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; and N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: 20 a). R 6 is not the same as R5; 0 -S I/S N b). when R 5 is a substituted heterocycle then it is not C13 alkyl. c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same time; d). the compound is not of the following structures: 230 WO 2012/082633 PCT/US2011/064441 o' o / F3C H NP HNP o Cl 0 C -NH S-NH o 0 F Br OMe s S-NH / -NH Cl 0 or 0
[2] 2. A compound according to claim 1, wherein: 5 R3 is C-R 7 R 4 is C-R 8 R 15 is C-R 1 6 ; and R 17 is C-R 8 . 10
[3] 3. A compound according to claim 1, wherein: R 3 is N or C-R R 4 is N or C-R 8 R 15 is N or C-R 16 ; and R 17 is N. 15
[4] 4. A compound according to claim 1, wherein: R 3 is C-R R 4 is C-R 8 R 6 is 2-benzofuran or 2-thienyl; 20 R 15 is C-R 1 6 ; and R 17 is C-R 8 . 231 WO 2012/082633 PCT/US2011/064441
[5] 5. A compound according to claim 4, wherein: R 6 is 2-benzofuran. 5
[6] 6. A compound according to claim 4, wherein: R 6 is 2-thienyl.
[7] 7. A compound according to claim 1, wherein: R 1 is H or substituted or unsubstituted C1.6 alkyl; 10 R 2 is H or substituted or unsubstituted C1.6 alkyl; R 3 is C-R R 4 is C-R
[8] 8 R 5 is substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 15 cycloalkenyl or is substituted or unsubstituted C610 aryl; R 6 is 2-benzofuran, 2 -thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 methylphenyl, or 4-chloro-3-trifluoromethylphenyl; R 15 is C-R 1 6 R 17 is N or C-R18 20 R 7 is H, substituted or unsubstituted C1.6 alkyl; R 8 is H, substituted or unsubstituted C1.6 alkyl; R 16 is H; and R 18 is H. 25 8. A compound according to claim 7, wherein: R 1 is H; R 2 is H; R 3 is C-R R 4 is C-R 8 30 R 5 is 2 thienyl, phenyl, phenyl-4-acetamide, 4-chloro-3-trifluoromethylphenyl, -1 methyl-1 H-imidazole, 3-pyridine, 2 aminophenyl, 1,3-dimethyl-1H-pyrazole, 1 methyl-1 H-pyrazole, 1-methyl-1 H-imidazole, 4-(1 H-pyrazol-1 -yl)phenyl, 1,3-thiazol 4-yl)phenyl, 232 WO 2012/082633 PCT/US2011/064441 4-(1,3-oxazol-5-yl)phenyl, 2-(methylamino)benzoate, 1-methyl-1 H-indole, 2 oxoindoline, 1-methyl-2,3-dioxoindoline, 1-methyl-2-oxoindoline, 2-furan, 4-biphenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, -3,5-dimethylisoxazole, 4-chloro-2,5 difluorophenyl, 5 4-(2-methylphenoxy)phenyl, 5-isoxazol-3-ylthiophene, 2,6-dichlorophenyl, 4 (methylsulfonyl)phenyl, 3,4-difluorophenyl, 4-chloro-3-methylphenyl, 2-oxo-2,3 dihydro-1,3-benzoxazole, 4-benzoic acid, 2-methoxybenzoic acid, 3-cyanophenyl, 4-tert-butylphenyl, 1,3-benzothiazole, 1 H-1,2,4-triazole, 2-chloro-1,3-benzothiazole, 2,4-dimethoxyphenyl, 2,5-dichloro-3-thienyl, 3-methoxyphenyl, 3 10 (methylsulfonyl)phenyl, 3-chloro-2-methylphenyl, 4phenylpropanoic acid, 2 ethoxybenzoic acid, 2-methylphenyl}acetamide, 3,5-bis(trifluoromethyl)phenyl, 1 H pyrazole, 4-(trifluoromethoxy)phenyl, 4-(benzyloxy)phenyl, 2-chloro-4-fluorobenzoic acid, thiophene-2-carboxylate, 4-fluorobenzoic acid, 2-chloro-quinoline, 2,3-dihydro 1 H-inden, 1 -nathphtyl, 1,3-benzodioxole, 3,5-dichloro-2-hydroxyphenyl, 2 15 benzofuran, quinoline, 4-methylbenzoate, 2,4-dimethyl-1,3-thiazole, 4-methyl-1,3 thiazol-2-yl}acetamide, 5-chloro-8-quinoline, 2,4,5-trifluorophenyl, 3,4 dimethoxyphenyl, 3,5-dimethyl-1H-pyrazole, 1-(phenylsulfonyl)-1H-pyrrole, N acetylindoline, 1,3,4-oxadiazol-2-yl-phenyl, 3-(1 -methyl-1 H-pyrazol-3-yl)phenyl, 2 thienylsulfonyl)amino]phenyl-4-methyl, 2-oxo-2H-chromene, 6-phenyl-3-pyridine, 2 20 chloro-4-(trifluoromethyl)phenyl, 6-phenoxypyridine, 5-phenylthiophene, 2,5 dimethyl-3-thienyl, 2-chlorophenyl-4-acetamide, (5-chloro-2,4-difluorophenyl, 4-(1 methyl-1 H-pyrazol-3-yl)phenyl, 5-methyl-1 -benzothiophene, 2,5-dimethylfuran, 4 (pyrrolidin-1-ylsulfonyl)phenyl, methyl-2-methyl-3-furoate, 3-oxo-3,4-dihydro-2H-1,4 benzoxazine, 2,4-dichloro-benzoic acid, 5-{[(dimethylamino) carbonyl]amino}- 2 25 ethoxyphenyl, 2-methoxyphenyl}acetamide, 2- imidazo[2,1-b][1,3]thiazole, 6 morpholin-4-ylpyridine, 3-[(6-methylpyrazin-2-yl)oxy]phenyl, 5-pyridin-2-ylthiophene, 3-pyrimidin-2-ylphenyl, 4-dihydro-2H-pyrido[3,2-b][1,4]oxazine, 6-(dimethylamino)-2 naphthyl, 2-(methylsulfonyl)phenyl, 3-methyl-8-quinoline, 5-isoxazol-5-ylthiophene, 5-(dimethylamino)-1-naphthyl, 2-chloro-thienyl, methyl, ethyl, benzyl, isso-butyl, 2,2 30 dimethylchromane, 2-oxo-2,3,4,5-tetrahydro-1 H-1 -benzazepine, 4-methyl-3,4 dihydro-2H-1,4-benzoxazine, 4-acetyl-3,4-dihydro-2H-1,4-benzoxazine, 4 (benzyloxy)phenyl, 2,4-dimethyl-1,3-thiazole, 3,5-dimethylisoxazole, 5-chloro-3 methyl-1-benzothien-2-yl, 2-chloro-4-fluorobenzoic acid, 4-methyl-1,3-thiazol-2 yl}acetamide, 1 H-1,2,4-triazole, phenyl}propanoic acid, 5-chlorothiophene-2 233 WO 2012/082633 PCT/US2011/064441 carboxylate, 3-phenylacetamide, 2-oxoindoline, 2-oxo-2,3-dihydro-1,3-benzoxazole, 5-isoxazol-3-yl-2-thienyl, 2-chloroquinoline, 1 -(phenylsulfonyl)-1 H-pyrrole, 2,5 dichloro-3-thienyl, 5-{[(dimethylamino)carbonyl]amino}-2-ethoxyphenyl, 6-morpholin 4-ylpyridine, 4-methoxythiophene, 3-furyl, 1-methyl-1 H-pyrazole, 6 5 chloroimidazo[2,1 -b][1,3]thiazole, 3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl, 3-pyrimidin-2-ylphenyl, 1-acetyl-indoline, isonicotinate, 3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl, 4-(3,5-dimethyl-1 H-pyrazol-1 yl)phenyl, 3,5-dimethyl-1 -phenyl-1 H-pyrazole, 4-methyl-3,4-dihydro-2H-1,4 benzoxazine, 3,4-dihydro-2H-1,5-benzodioxepine, 2,2-dimethylchromane, 4-methyl 10 2-phenyl-1,3-thiazole, 5-pyridin-2-yl-2-thienyl, 4-methyl-3,4-dihydro-2H-pyrido[3,2 b][1,4]oxazine, 3-oxo-3,4-dihydro-2H-1,4-benzoxazine, 5,6-dichloro-3-pyridine, 2,3 dioxo-1,2,3,4-tetrahydroquinoxaline or 4-acetyl-3,4-dihydro-2H-1,4-benzoxazine; R 6 is 2-benzofuran, 2-thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 methylphenyl, or 4-chloro-3-trifluoromethylphenyl; 15 R 15 is C-R 1 6 ; R 17 is N or C-R18 R 7 is H, methyl or chlorine; R 8 is H or chlorine; R 16 is H; and 20 R 18 is H.
[9] 9. A compound according to claim 1, selected from: N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; 25 N-{4,5-dichloro-2-[(phenylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}acetamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 methylphenyl]thiophene-2-sulfonamide; 30 N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -methyl-1 H imidazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 methylphenyl]pyridine-3-sulfonamide; 234 WO 2012/082633 PCT/US2011/064441 N-(2-{[(4-aminophenyl)sulfonyl]am ino}-5-chlorophenyl)-4-chloro-3 (trifluoromethyl)benzenesulfonam ide; 5-chloro-N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 methylphenyl]-1,3-dimethyl-1 H-pyrazole-4-sulfonamide; 5 N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 1,3,5-trimethyl-1 H-pyrazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 1-methyl-1 H-pyrazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 10 1-methyl-1 H-imidazole-4-sulfonamide; 4-chloro-N-{4-chloro-5-methyl-2-[(phenylsulfonyl)am ino] phenyl}-3 (trifluoromethyl)benzenesulfonamide; 4-chloro-N-{5-chloro-2-[(phenylsulfonyl)amino]phenyl}-3 (trifluoromethyl)benzenesulfonamide; 15 N-[4,5-dichloro-2-({[4-(1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[4-(1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene 20 2-sulfonamide; N-[4,5-dichloro-2-({[4-(2-methyl-1,3-thiazol-4 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[4-(2-methyl-1,3-thiazol-4 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 25 N-[4,5-dichloro-2-({[4-(1,3-oxazol-5-yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 (methylam ino)benzoate; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 30 (methylamino)benzoic acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-1 H-indole-5 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxoindoline-5-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxoindoline-5-sulfonamide; 235 WO 2012/082633 PCT/US2011/064441 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-2,3-dioxoindoline-5 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-2-oxoindoline-5 sulfonamide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-2-sulfonamide; N-{2-[(biphenyl-4-ylsulfonyl)amino]-4,5-d ichlorophenyl}th iophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(3,5-difluorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3,5-dichlorophenyl)sulfonyl]amino}phenyl)th iophene-2 10 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-3,5-d methyl isoxazole-4 sulfonamide; N-(4,5-d ichloro-2-{[(4-chloro-2,5-d ifluorophenyl)sulfonyl]am ino}phenyl)th iophene-2 sulfonamide; 15 N-[4,5-dichloro-2-({[4-(2-methylphenoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-5-isoxazol-3-ylth iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2,4-dimethylphenyl)sulfonyl]am ino}phenyl)th iophene-2 20 sulfonamide; N-(4,5-d ichloro-2-{[(2,6-dichlorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-fluorophenyl)sulfonyl]am ino}phenyl)th iophene-2-sulfonam ide; N-[4,5-dichloro-2-({[4-(methylsulfonyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 25 sulfonamide; N-(4,5-d ichloro-2-{[(3,4-difluorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-methyl-1 30 benzothiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(4-chloro-3-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3-dihydro-1,3 benzoxazole-6-sulfonamide; 236 WO 2012/082633 PCT/US2011/064441 4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methoxybenzoic acid; N-(4,5-d ichloro-2-{[(3-chloro-4-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 5 sulfonamide; N-(4,5-dichloro-2-{[(3-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(4-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; N-(2-{[(4-tert-butylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2 sulfonamide; 10 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzothiazole-6 sulfonamide; N-(4,5-dichloro-2-{[(2-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 H-1,2,4-triazole-5-sulfonamide; 15 2-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzothiazole-6 sulfonamide; N-(4,5-dichloro-2-{[(3,4-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2,4-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 20 sulfonamide; N-(4,5-dichloro-2-{[(2,5-dichloro-3-thienyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 N-[4,5-dichloro-2-({[4-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[3-(methylsulfonyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 30 sulfonamide; N-(4,5-d ichloro-2-{[(3-chloro-2-methyl phenyl)sulfonyl]am ino}phenyl)thiophene-2 sulfonamide; 3-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}propanoic acid; 237 WO 2012/082633 PCT/US2011/064441 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}am ino)sulfonyl]-2-ethoxybenzoic acid; N-{4-[({4,5-d ichloro-2-[(2-th ienylsulfonyl)am ino]phenyl}am ino)sulfonyl]-2 methylphenyl}acetam ide; 5 N-[2-({[3,5-bis(trifluoromethyl)phenyl]sulfonyl}amino)-4,5-dichlorophenyl]thiophene 2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 H-pyrazole-4-sulfonamide; N-(4,5-dichloro-2-{[(3-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[4-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 10 sulfonamide; N-[2-({[4-(benzyloxy)phenyl]sulfonyl}amino)-4,5-dichlorophenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 2-chloro-5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 15 fluorobenzoic acid; methyl 5-chloro-3-[({4,5-dichloro-2-[(2 thienylsulfonyl)am ino] phenyl}am ino)sulfonyl]th iophene-2-carboxylate; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4-fluorobenzoic acid; 20 2-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-6-sulfonamide; N-(4,5-dichloro-2-{[(5-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2,3-dihydro-1 H-inden-5-ylsulfonyl)amino]phenyl}thiophene-2 sulfonamide; 25 N-(4,5-dichloro-2-{[(4-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(1 -naphthylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzodioxole-5-sulfonamide; N-[4,5-dichloro-2-({[2-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; 30 N-(4,5-dichloro-2-{[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]amino}phenyl)thiophene 2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-5-sulfonamide; N-(4,5-dichloro-2-{[(2,6-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 238 WO 2012/082633 PCT/US2011/064441 N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}qu inol ine-3-sulfonam ide; N-(4,5-d ichloro-2-{[(2,3-dichlorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; methyl 4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoate; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-8-sulfonamide; N-(4,5-dichloro-2-{[(2-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-2,4-dimethyl-1,3-thiazole-5 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 10 sulfonamide; N-{5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4-methyl-1 ,3 thiazol-2-yl}acetamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}isoquinoline-5-sulfonamide; 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-8-sulfonamide; 15 N-(4,5-dichloro-2-{[(2,5-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2,4,5-trifluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 20 sulfonamide; N-(4,5-dichloro-2-{[(2-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[3-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; 25 methyl 3-[({4,5-dichloro-2-[(2 thienylsulfonyl)am ino] phenyl}am ino)sulfonyl]th iophene-2-carboxylate; N-(4,5-dichloro-2-{[(2,5-difluorophenyl)sulfonyl]amino}pheny)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,5-dimethyl-1 H-pyrazole-4 30 sulfonamide; N-(4,5-dichloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-6-sulfonamide; 239 WO 2012/082633 PCT/US2011/064441 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -(phenylsulfonyl)-1 H-pyrrole-3 sulfonamide; N-(4,5-dichloro-2-{[(3,5-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 5 N-(4,5-dichloro-2-{[(4-methoxy-3-methylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-pyrazole-5 10 sulfonamide; 1 -acetyl-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}indoline-5-sulfonamide; N-[4,5-dichloro-2-({[3-(5-methyl-1,3,4-oxadiazol-2 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[3-(1 -methyl-1 H-pyrazol-3 15 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-4-methyl-2-phenyl-1,3-thiazole 5-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-methylbenzoic 20 acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-1,2,3,4 tetrahydroquinoline-6-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2H-chromene-6 sulfonamide; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-phenylpyridine-3-sulfonamide; ethyl 3-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]isonicotinate; N-[4,5-dichloro-2-({[2-chloro-4 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 30 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-1 -benzofuran-5 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-phenoxypyridine-3 sulfonamide; 240 WO 2012/082633 PCT/US2011/064441 N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)am ino]phenyl}-5-phenylth iophene-2 sulfonamide; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}am ino)sulfonyl]-4-methylbenzoic acid; 5 N-(4,5-dichloro-2-{[(2,5-dimethyl-3-thienyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{2-chloro-4-[({4,5-d ichloro-2-[(2 thienylsulfonyl)amino]phenyl}am ino)sulfonyl]phenyl}acetam ide; N-(4,5-d ichloro-2-{[(5-chloro-2,4-d ifluorophenyl)sulfonyl]am ino}phenyl)th iophene-2 10 sulfonamide; N-[4,5-dichloro-2-({[4-(1 -methyl-1 H-pyrazol-3 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methyl-1 -benzothiophene-2 sulfonamide; 15 N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-2,5-dimethylfuran-3-sulfonamide; N-[4,5-dichloro-2-({[4-(pyrrolidin-1 ylsulfonyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-methyl 3-furoate; 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-oxo-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; 2,4-dichloro-5-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; N-[4,5-dichloro-2-({[4-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 25 sulfonamide; N-(4,5-d ichloro-2-{[(5-{[(d imethylam ino)carbonyl]amino}-2 ethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methoxyphenyl}acetamide; 30 6-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}imidazo[2,1 b][1,3]thiazole-5-sulfonamide; N-[4,5-dichloro-2-({[3-(i -methyl-1 H-pyrazol-5 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 241 WO 2012/082633 PCT/US2011/064441 methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-1 -methyl 1 H-pyrrole-2-carboxylate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methylfuran-2-sulfonamide; N-[4,5-dichloro-2-({[4-(phenoxymethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 5 sulfonamide; N-(4,5-dichloro-2-{[(4-phenoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 5,6-dichloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3 sulfonamide; 10 N-(4,5-dichloro-2-{[(2-fluoro-4-methylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2-ethoxy-5 {[(methylamino)carbonyl]am ino}phenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 15 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-morpholin-4-ylpyridine-3 sulfonamide; N-{4,5-d ichloro-2-[({3-[(6-methylpyrazin-2 yl)oxy]phenyl}sulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}chromane-6-sulfonamide; 20 N-[4,5-dichloro-2-({[4-(3,5-dimethyl-1 H-pyrazol-1 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methylthiophene-2 sulfonamide; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 25 hydroxybenzoic acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2,4-dichloro-5-methyl phenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; 30 N-[4,5-dichloro-2-({[4-fluoro-3 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoate; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxyth iophene-3-carboxylate; 242 WO 2012/082633 PCT/US2011/064441 methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 furoate; N-(4,5-dichloro-2-{[(2-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-1 H-pyrazole-3 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-1 H-indole-7 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-pyridin-2-ylthiophene-2 10 sulfonamide; N-(4,5-dichloro-2-{[(4'-fluorobiphenyl-4-yl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-fluoro-4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 15 N-(4,5-dichloro-2-{[(3-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3-dihydro-1,3 benzothiazole-6-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-3-sulfonamide; 20 N-[4,5-dichloro-2-({[3-(5-methyl-1,2,4-oxadiazol-3 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; ethyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-3-furoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,4-dihydro-2H-1,5 benzodioxepine-7-sulfonamide; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-1 -benzofuran-7 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-methyl-1,3-benzothiazole-6 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}- 1,3,5-trimethyl-1 H-pyrazole-4 30 sulfonamide; N-(4,5-dichloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-cyano-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 243 WO 2012/082633 PCT/US2011/064441 N-{5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-1,3-thiazol-2 yI}acetamide; N-{4,5-d ichloro-2-[({4-[(6-methylpyrazin-2 yl)oxy]phenyl}sulfonyl)am ino]phenyl}thiophene-2-sulfonamide; 5 N-(4,5-dichloro-2-{[(3-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxybenzoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-3 10 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-4-methyl-3,4-dihydro-2H pyrido[3,2-b][1,4]oxazine-7-sulfonamide; 5-chloro-N-{4,5-dichloro-2-[(2-thienysulfonyl)amino]phenyl}-1,3-dimethyl-1 H pyrazole-4-sulfonamide; 15 N-(4,5-dichloro-2-{[(5-chloro-2-naphthyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{2-[(biphenyl-3-ylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(2-fluoro-5-methyl phenyl)sulfonyl]am ino}phenyl)th iophene-2 sulfonamide; 20 4-chloro-3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxybenzoic acid; N-[4,5-dichloro-2-({[4-(pyridin-2-yloxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 25 sulfonamide; N-{4,5-dichloro-2-[(2-naphthylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; N-[4,5-dichloro-2-({[6-(d imethylam ino)-2-naphthyl]sulfonyl}am ino)phenyl]th iophene 2-sulfonamide; 30 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; N-(4,5-dichloro-2-{[(4'-chlorobiphenyl-4-yl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(2-{[(3-acetylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2-sulfonamide; 244 WO 2012/082633 PCT/US2011/064441 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dioxo-1,2,3,4 tetrahydroquinoxaline-6-sulfonamide; N-{4-[({4,5-d ich loro-2-[(2 thienylsulfonyl)amino]phenyl}am ino)sulfonyl]benzyl}acetam ide; 5 N-[4,5-dichloro-2-({[3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[2-(methylsulfonyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-3-methylqu inol ine-8 10 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-2,3-dihydro-1,4-benzodioxine-6 sulfonamide; N-[4,5-dichloro-2-({[3-(2-methylpyrim id in-4 yl)phenyl]sulfonyl}amino)phenyl]th iophene-2-sulfonam ide; 15 6-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-6-methoxypyrid ine-3 sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methylbenzoate; 20 N-(4,5-dichloro-2-{[(2,5-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(2-{[(4-acetylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2-sulfonamide; methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methylbenzoate; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-isoxazol-5-ylthiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-(1,3-oxazol-5-yl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(5-chloro-2-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 30 sulfonamide; N-[4,5-dichloro-2-({[5-(dimethylamino)-1 -naphthyl]sulfonyl}amino)phenyl]thiophene 2-sulfonamide; methyl 2-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxybenzoate; 245 WO 2012/082633 PCT/US2011/064441 5-chloro-N-{4,5-d ichloro-2-[(2-thienylsulfonyl)am ino]phenyl}th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(4-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; 5 N-{4,5-dichloro-2-[(methylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(3,5-dichloro-4-hydroxyphenyl)sulfonyl]am ino}phenyl)th iophene 2-sulfonamide; N-[4,5-dichloro-2-({[4-chloro-3 (trifluoromethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2-sulfonam ide; 10 2-chloro-5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; N-[4,5-dichloro-2-({[4-(pyridin-3-yloxy)phenyl]sulfonyl}am ino)phenyl]thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-imidazole-4 15 sulfonamide; N-{4,5-d ichloro-2-[(ethylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-(4,5-dichloro-2-{[(4-chloro-2-fluoro-5 methylphenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-fluorobenzoic 20 acid; N-{2-[(biphenyl-2-ylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide; N-{3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methylphenyl}acetamide; N-(2-{[(5-tert-butyl-2-methylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2 25 sulfonamide; N-{2-[(benzylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide N-{4,5-dichloro-2-[(isobutylsulfonyl)amino]phenyl}thiophene-2-sulfonamide N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-2,2-d imethylchromane-6 sulfonamide; 30 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,2-dimethyl-1 H-imidazole-4 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3,4,5-tetrahydro-1 H-1 benzazepine-7-sulfonamide; 246 WO 2012/082633 PCT/US2011/064441 N-(4,5-d ichloro-2-{[(4-cyclohexylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; 4-chloro-N-1 -- {4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}benzene-1,3 disulfonamide; 5 N-(4,5-dichloro-2-{[(4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{3-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}acetamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-indole-4 sulfonamide; 10 N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(5,6,7,8-tetrahydronaphthalen-2 15 ylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[4-(2-chlorophenoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 20 N-(4,5-dichloro-2-{[(2-methylphenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 2-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenoxy}acetamide; N-(4,5-dichloro-2-{[(2,4-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,5-dimethyl-1 -phenyl-1 H pyrazole-4-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-4-methyl-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; 2-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; 30 4-acetyl-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; N-(4,5-dichloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{5-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 247 WO 2012/082633 PCT/US2011/064441 N-{4-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{5-chloro-2-[(methylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-imidazole-4 sulfonamide; 5 N-{2-[(benzylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; N-(5-chloro-2-{[(3-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(4-chlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; 15 N-{5-chloro-2-[(2-naphthylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-8-sulfonamide; N-(5-chloro-2-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,4-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-{2-[(biphenyl-4-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-[5-chloro-2-({[4-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 25 sulfonamide; N-[5-chloro-2-({[4-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 30 N-{5-chloro-2-[(1 -naphthylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2-chlorophenyl)sulfonyl]am ino}phenyl)-1 -benzofuran-2-sulfonamide; N-[5-chloro-2-({[3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 248 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(2-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5 N-(5-chloro-2-{[(3,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(2-{[(4-tert-butylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; N-[2-({[4-(benzyloxy)phenyl]sulfonyl}amino)-5-chlorophenyl]-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3-benzodioxole-5 sulfonamide; 15 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,4-dimethyl-1,3-thiazole-5 sulfonamide; N-[5-chloro-2-({[3-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-(5-chloro-2-{[(3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{5-chloro-2-[(2-furylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzothien-3-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 25 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3-benzothiazole-6 sulfonamide; N-[5-chloro-2-({[3-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 30 N-(5-chloro-2-{[(2-fluorophenyl)sulfonyl]am ino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2,5-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[2-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 249 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(5-chloro-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5 methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]th iophene-2-carboxylate; N-{5-chloro-2-[(ethylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethylisoxazole-4 sulfonamide; 10 N-(5-chloro-2-{[(5-chloro-3-methyl-1 -benzothien-2-yl)sulfonyl]amino}phenyl)-1 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 15 sulfonamide; N-{5-chloro-2-[(isobutylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 5-[({2-[(i -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2-chloro-4 fluorobenzoic acid; N-{5-[({2-[(i -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 20 methyl-1,3-thiazol-2-yl}acetamide; N-(5-chloro-2-{[(2,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4-chloro-2,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 25 N-(5-chloro-2-{[(4-chloro-3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(i -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 H-1,2,4-triazole-5 sulfonamide; 3-{4-[({2-[(i -benzofuran-2-ylsulfonyl)amino]-4 30 chlorophenyl}amino)sulfonyl]phenyl}propanoic acid; methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-5 chlorothiophene-2-carboxylate; N-{2-[(i -benzofuran-5-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 sulfonamide; 250 WO 2012/082633 PCT/US2011/064441 N-{3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]phenyl}acetamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxoindoline-5 sulfonamide; 5 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethyl-1 H-pyrazole 4-sulfonamide; N-[5-chloro-2-({[4-(2-methylphenoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3-dihydro-1,3 10 benzoxazole-6-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloro-1,3-benzothiazole 6-sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 ethoxybenzoic acid; 15 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 fluorobenzoic acid; N-(5-chloro-2-{[(2,6-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}isoquinoline-5-sulfonamide; 20 N-(5-chloro-2-{[(2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(5-isoxazol-3-yl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 25 sulfonamide; 4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]benzoic acid; N-(5-chloro-2-{[(3,4-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 30 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]benzoic acid; N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylphenyl}acetamide; 251 WO 2012/082633 PCT/US2011/064441 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloroquinoline-6 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-3-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5-chloroquinoline-8 5 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-6-sulfonamide; N-(5-chloro-2-{[(2,4-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 10 methoxybenzoic acid; N-(5-chloro-2-{[(2,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[2-({[3,5-bis(trifluoromethyl)phenyl]sulfonyl}amino)-5-chlorophenyl]-1 -benzofuran 2-sulfonamide; 15 N-(5-chloro-2-{[(5-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide N-(5-chloro-2-{[(2,3-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-(5-chloro-2-{[(2,5-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -(phenylsulfonyl)-1 H pyrrole-3-sulfonamide; 25 N-(5-chloro-2-{[(2,6-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chloro-4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[2-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 30 sulfonamide; N-(5-chloro-2-{[(2,5-dichloro-3-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 H-pyrazole-4 sulfonamide; 252 WO 2012/082633 PCT/US2011/064441 N-{5-chloro-2-[(2,3-dihydro-1 H-inden-5-ylsulfonyl)amino]phenyl}-1 -benzofuran-2 sulfonamide; methyl 4-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]benzoate; 5 N-(5-chloro-2-{[(2,4,5-trifluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4-methoxy-3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-1,2,3,4 tetrahydroquinoline-6-sulfonamide; N-(5-chloro-2-{[(5-{[(dimethylamino)carbonyl]amino}-2 ethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; 15 N-(5-chloro-2-{[(2-ethoxy-5 {[(methylamino)carbonyl]amino}phenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(2-{[(4-acetylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2-sulfonamide; methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 20 chlorophenyl}amino)sulfonyl]benzoate; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3-dihydro-1,3 benzothiazole-6-sulfonamide; N-{5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-1,3 thiazol-2-yl}acetamide; 25 N-(5-chloro-2-{[(3-chloro-4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2H-chromene-6 sulfonamide; N-(5-chloro-2-{[(5-chloro-2,4-difluorophenyl)sulfony]amino}phenyl)-1 -benzofuran-2 30 sulfonamide; N-{5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methoxyphenyl}acetamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-morpholin-4-ylpyridine-3 sulfonamide; 253 WO 2012/082633 PCT/US2011/064441 methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxyth iophene-3-carboxylate; N-{5-chloro-2-[(3-furylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{5-chloro-2-[({4-[(6-methylpyrazin-2-yl)oxy]phenyl}sulfonyl)amino]phenyl}-1 5 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-pyrazole-5 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-phenylpyridine-3 sulfonamide; 10 N-[5-chloro-2-({[4-(1 -methyl-1 H-pyrazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-chloroimidazo[2, 1 b][1,3]thiazole-5-sulfonamide; N-{5-chloro-2-[({3-[(6-methylpyrazin-2-yl)oxy]phenyl}sulfonyl)amino]phenyl}-1 15 benzofuran-2-sulfonamide; methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 furoate; N-[5-chloro-2-({[3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 20 N-(5-chloro-2-{[(3-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 1 -acetyl-N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}indoline-5 sulfonamide; ethyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 25 chlorophenyl}amino)sulfonyl]isonicotinate; N-(5-chloro-2-{[(5-methyl-1 -benzothien-2-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[3-(1 -methyl-1 H-pyrazol-5-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 30 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}chromane-6-sulfonamide; N-(5-chloro-2-{[(2-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; ethyl 5-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-3 furoate; 254 WO 2012/082633 PCT/US2011/064441 methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxybenzoate; N-(5-chloro-2-{[(4-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)-1-benzofuran-2 sulfonamide; 5 N-[5-chloro-2-({[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-[5-chloro-2-({[2-chloro-4-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2,5-dimethyl-3-furyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; methyl 5-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-1 methyl-1 H-pyrrole-2-carboxylate; N-[5-chloro-2-({[4-(3,5-dimethyl-1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 15 N-(5-chloro-2-{[(4-chloro-2-fluoro-5-methylphenyl)sulfonyl]amino}phenyl)-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-pyrazole-3 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethyl-1 -phenyl-1 H 20 pyrazole-4-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-3,4-dihydro-2H 1,4-benzoxazine-6-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,4-dihydro-2H-1,5 benzodioxepine-7-sulfonamide; 25 N-[5-chloro-2-({[3-(1 -methyl-1 H-pyrazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{5-chloro-2-[(2,3-dihydro-1 -benzofuran-5-ylsulfonyl)amino]phenyl}-1 -benzofuran 2-sulfonamide; N-[5-chloro-2-({[4-(pyrrolidin-1 -ylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 30 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(5-methyl-2-furyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(5-methyl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 255 WO 2012/082633 PCT/US2011/064441 N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-indole-7 sulfonamide; N-{5-chloro-2-[(2,3-dihydro-1 -benzofuran-7-ylsulfonyl)amino]phenyl}-1 -benzofuran 2-sulfonamide; 5 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,2-dimethylchromane-6 sulfonamide; N-[5-chloro-2-({[4-(2-methyl-1,3-thiazol-4-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-2-phenyl-1 ,3 10 thiazole-5-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-phenoxypyridine-3 sulfonamide; methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methyl-3-furoate; 15 N-[5-chloro-2-({[4-(phenoxymethyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 hydroxybenzoic acid; N-(5-chloro-2-{[(5-pyridin-2-yl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-methyl-1,3 benzothiazole-6-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-3,4-dihydro-2H pyrido[3,2-b][1,4]oxazine-7-sulfonamide; 25 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-indole-4 sulfonamide; N-(5-chloro-2-{[(5-phenyl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3-oxo-3,4-dihydro-2H-1,4 30 benzoxazine-6-sulfonamide; N-(5-chloro-2-{[(4-phenoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzothien-2-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 sulfonamide; 256 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(4'-fluorobiphenyl-4-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3,5-trimethyl-1 H pyrazole-4-sulfonamide; 5 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5-chloro-1,3-dimethyl-1 H pyrazole-4-sulfonamide; 2-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]phenoxy}acetamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 10 methylbenzoic acid; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methylbenzoic acid; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2,4 dichlorobenzoic acid; 15 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5,6-dichloropyridine-3 sulfonamide; N-(5-chloro-2-{[(2,4-dichloro-5-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran 2-sulfonamide; N-(5-chloro-2-{[(3-fluoro-4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-(5-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 25 N-(5-chloro-2-{[(2,5-dimethyl-3-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2-fluoro-4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 30 sulfonamide; N-[5-chloro-2-({[4-fluoro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 257 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(3-cyano-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(5-chloro-2-naphthyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5 N-{2-[(biphenyl-3-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloropyridine-3 sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}pyridine-3-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,3-dihydro-1,4 10 benzodioxine-6-sulfonamide; N-(5-chloro-2-{[(5-isoxazol-5-yl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-dichloro-4-hydroxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran 2-sulfonamide; 15 5-[({2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 fluorobenzoic acid; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,2-dimethyl-1 H-imidazole 4-sulfonamide; N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 20 sulfonamide; N-(5-chloro-2-{[(2-fluoro-5-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4'-chlorobiphenyl-4-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 25 N-[5-chloro-2-({[3-(2-methylpyrimidin-4-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-[5-chloro-2-({[5-(1,3-oxazol-5-yl)-2-thienyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 30 benzofuran-2-sulfonamide; N-{2-[(biphenyl-2-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3,4,5-tetrahydro 1 H-1 -benzazepine-7-sulfonamide; 258 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(3-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 chlorobenzoic acid; 5 N-(2-{[(3-acetylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-chloropyridine-3 sulfonamide; N-(5-chloro-2-{[(5-chloro-2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 10 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 chlorobenzoic acid; N-{3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methylphenyl}acetamide; N-(5-chloro-2-{[(4-cyclohexylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 15 sulfonamide; N-{5-chloro-2-[(5,6,7,8-tetrahydronaphthalen-2-ylsulfonyl)amino]phenyl}-1 benzofuran-2-sulfonamide; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxybenzoic acid; 20 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,3-dioxo-1,2,3,4 tetrahydroquinoxaline-6-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-methoxypyridine-3 sulfonamide; 4-acetyl-N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,4-dihydro-2H 25 1,4-benzoxazine-6-sulfonamide; N-[5-chloro-2-({[5-(dimethylamino)-1 -naphthyl]sulfonyl}amino)phenyl]-1 -benzofuran 2-sulfonamide; N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 chlorophenyl}acetamide; 30 N-[5-chloro-2-({[4-(pyridin-3-yloxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(2-{[(5-tert-butyl-2-methylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 sulfonamide; 259 WO 2012/082633 PCT/US2011/064441 N-1 -- {2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-chlorobenzene-1,3 disulfonamide; N-[5-chloro-2-({[4-(2-chlorophenoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 5 N-[5-chloro-2-({[4-(pyridin-2-yloxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]benzyl}acetamide; methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 10 methylbenzoate; methyl 2-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxybenzoate; methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylbenzoate; 15 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3-methylquinoline-8 sulfonamide; N-[5-chloro-2-({[6-(dimethylamino)-2-naphthyl]sulfonyl}amino)phenyl]-1 -benzofuran 2-sulfonamide; N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 20 sulfonamide; and N-[5-chloro-3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2 yl]thiophene-2-sulfonamide.
[10] 10. A pharmaceutical composition comprising as active ingredient a 25 therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable adjuvant, diluents or carrier.
[11] 11. A pharmaceutical composition according to claim 10 wherein the compound is selected from: 30 N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(phenylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}acetamide; 260 WO 2012/082633 PCT/US2011/064441 N-[5-chloro-2-({[4-chloro-3-(trifl uoromethyl)phenyl]sulfonyl}am ino)-4 methylphenyl]th iophene-2-sulfonam ide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -methyl-1 H imidazole-4-sulfonamide; 5 N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 methylphenyl]pyridine-3-sulfonamide; N-(2-{[(4-aminophenyl)sulfonyl]amino}-5-chlorophenyl)-4-chloro-3 (trifluoromethyl)benzenesulfonamide; 5-chloro-N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4 10 methylphenyl]-1,3-dimethyl-1 H-pyrazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 1,3,5-trimethyl-1 H-pyrazole-4-sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 1-methyl-1 H-pyrazole-4-sulfonamide; 15 N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)-4-methylphenyl] 1-methyl-1 H-imidazole-4-sulfonamide; 4-chloro-N-{4-chloro-5-methyl-2-[(phenylsulfonyl)am ino] phenyl}-3 (trifluoromethyl)benzenesulfonamide; 4-chloro-N-{5-chloro-2-[(phenylsulfonyl)amino]phenyl}-3 20 (trifluoromethyl)benzenesulfonamide; N-[4,5-dichloro-2-({[4-(1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[4-(1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; 25 N-[4-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene 2-sulfonamide; N-[4,5-dichloro-2-({[4-(2-methyl-1,3-thiazol-4 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[4-(2-methyl-1,3-thiazol-4 30 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[4-(1,3-oxazol-5-yl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 (methylam ino)benzoate; 261 WO 2012/082633 PCT/US2011/064441 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}am ino)sulfonyl]-2 (methylamino)benzoic acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-l-methyl-1 H-indole-5 sulfonamide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxoindoline-5-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxoindoline-5-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-2,3-dioxoindoline-5 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-2-oxoindoline-5 10 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-2-sulfonamide; N-{2-[(biphenyl-4-ylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide; N-(4,5-dichloro-2-{[(3,5-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 15 N-(4,5-dichloro-2-{[(3,5-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-3,5-di methyl isoxazole-4 sulfonamide; N-(4,5-dichloro-2-{[(4-chloro-2,5-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 20 sulfonamide; N-[4,5-dichloro-2-({[4-(2-methylphenoxy)phenyl]sulfonyl}amino)phenyl]th iophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-isoxazol-3-ylthiophene-2 sulfonamide; 25 N-(4,5-dichloro-2-{[(2,4-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2,6-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 30 N-[4,5-dichloro-2-({[4-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3,4-difluorophenyl)sulfonyl]amino}pheny)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; 262 WO 2012/082633 PCT/US2011/064441 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-methyl-1 benzothiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(4-chloro-3-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3-dihydro-1,3 benzoxazole-6-sulfonamide; 4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methoxybenzoic acid; 10 N-(4,5-dichloro-2-{[(3-chloro-4-methylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(4-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; N-(2-{[(4-tert-butylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2 15 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzothiazole-6 sulfonamide; N-(4,5-dichloro-2-{[(2-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 H-1,2,4-triazole-5-sulfonamide; 2-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzothiazole-6 sulfonamide; N-(4,5-dichloro-2-{[(3,4-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 N-(4,5-dichloro-2-{[(2,4-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2,5-dichloro-3-thienyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 30 sulfonamide; N-[4,5-dichloro-2-({[4-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 263 WO 2012/082633 PCT/US2011/064441 N-[4,5-dichloro-2-({[3-(methylsulfonyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; 5 3-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}propanoic acid; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-ethoxybenzoic acid; N-{4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 10 methylphenyl}acetamide; N-[2-({[3,5-bis(trifluoromethyl)phenyl]sulfonyl}amino)-4,5-dichlorophenyl]thiophene 2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 H-pyrazole-4-sulfonamide; N-(4,5-dichloro-2-{[(3-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 15 N-[4,5-dichloro-2-({[4-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-[2-({[4-(benzyloxy)phenyl]sulfonyl}amino)-4,5-dichlorophenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 20 2-chloro-5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 fluorobenzoic acid; methyl 5-chloro-3-[({4,5-dichloro-2-[(2 thienylsulfonyl)am ino] phenyl}am ino)sulfonyl]th iophene-2-carboxylate; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4-fluorobenzoic 25 acid; 2-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-6-sulfonamide; N-(4,5-dichloro-2-{[(5-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2,3-dihydro-1 H-inden-5-ylsulfonyl)amino]phenyl}thiophene-2 30 sulfonamide; N-(4,5-dichloro-2-{[(4-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(1 -naphthylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,3-benzodioxole-5-sulfonamide; 264 WO 2012/082633 PCT/US2011/064441 N-[4,5-dichloro-2-({[2-(trifluoromethoxy)phenyl]sulfonyl}am ino)phenyl]thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]am ino}phenyl)th iophene 2-sulfonamide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-5-sulfonamide; N-(4,5-dichloro-2-{[(2,6-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-3-sulfonamide; N-(4,5-dichloro-2-{[(2,3-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 10 sulfonamide; methyl 4-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-8-sulfonamide; N-(4,5-dichloro-2-{[(2-chlorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-2,4-dimethyl-1,3-thiazole-5 15 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4-methyl-1 ,3 thiazol-2-yl}acetamide; 20 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}isoquinoline-5-sulfonamide; 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-8-sulfonamide; N-(4,5-dichloro-2-{[(2,5-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2,4,5-trifluorophenyl)sulfonyl]amino}phenyl)thiophene-2 25 sulfonamide; N-(4,5-dichloro-2-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 30 N-[4,5-dichloro-2-({[3-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; methyl 3-[({4,5-dichloro-2-[(2 thienylsulfonyl)am ino] phenyl}am ino)sulfonyl]th iophene-2-carboxylate; 265 WO 2012/082633 PCT/US2011/064441 N-(4,5-d ichloro-2-{[(2,5-difluorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,5-dimethyl-1 H-pyrazole-4 sulfonamide; 5 N-(4,5-dichloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}quinoline-6-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -(phenylsulfonyl)-1 H-pyrrole-3 sulfonamide; 10 N-(4,5-dichloro-2-{[(3,5-dimethylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(4-methoxy-3-methyl phenyl)sulfonyl]am ino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 15 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-pyrazole-5 sulfonamide; 1 -acetyl-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}indoline-5-sulfonamide; N-[4,5-dichloro-2-({[3-(5-methyl-1,3,4-oxadiazol-2 20 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[3-(1 -methyl-1 H-pyrazol-3 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-4-methyl-2-phenyl-1,3-thiazole 5-sulfonamide; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-methylbenzoic acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-1,2,3,4 tetrahydroquinoline-6-sulfonamide; 30 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2H-chromene-6 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-phenylpyridine-3-sulfonamide; ethyl 3-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]isonicotinate; 266 WO 2012/082633 PCT/US2011/064441 N-[4,5-dichloro-2-({[2-chloro-4 (trifluoromethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2-sulfonam ide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-1 -benzofuran-5 sulfonamide; 5 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-phenoxypyridine-3 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)am ino]phenyl}-5-phenylth iophene-2 sulfonamide; 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}am ino)sulfonyl]-4-methylbenzoic 10 acid; N-(4,5-d ichloro-2-{[(2,5-dimethyl-3-th ienyl)sulfonyl]am ino}phenyl)thiophene-2 sulfonamide; N-{2-chloro-4-[({4,5-d ichloro-2-[(2 thienylsulfonyl)amino]phenyl}am ino)sulfonyl]phenyl}acetam ide; 15 N-(4,5-dichloro-2-{[(5-chloro-2,4-difluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[4-(1 -methyl-1 H-pyrazol-3 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methyl-1 -benzothiophene-2 20 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)am ino]phenyl}-2,5-d imethylfuran-3-sulfonamide; N-[4,5-dichloro-2-({[4-(pyrrolidin-1 ylsulfonyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-methyl 25 3-furoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-oxo-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; 2,4-dichloro-5-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 30 N-[4,5-dichloro-2-({[4-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(5-{[(d imethylam ino)carbonyl]amino}-2 ethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 267 WO 2012/082633 PCT/US2011/064441 N-{5-[({4,5-d ichloro-2-[(2-th ienylsulfonyl)am ino]phenyl}am ino)sulfonyl]-2 methoxyphenyl}acetam ide; 6-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}imidazo[2, 1 b][1,3]thiazole-5-sulfonamide; 5 N-[4,5-dichloro-2-({[3-(l -methyl-1 H-pyrazol-5 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-1 -methyl 1 H-pyrrole-2-carboxylate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methylfuran-2-sulfonamide; 10 N-[4,5-dichloro-2-({[4-(phenoxymethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(4-phenoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 5,6-dichloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3 15 sulfonamide; N-(4,5-d ichloro-2-{[(2-fluoro-4-methyl phenyl)sulfonyl]am ino}phenyl)th iophene-2 sulfonamide; N-(4,5-dichloro-2-{[(2-ethoxy-5 {[(methylamino)carbonyl]am ino}phenyl)sulfonyl]amino}phenyl)thiophene-2 20 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-morpholin-4-ylpyridine-3 sulfonamide; N-{4,5-d ichloro-2-[({3-[(6-methylpyrazin-2 yl)oxy]phenyl}sulfonyl)amino]phenyl}thiophene-2-sulfonamide; 25 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}chromane-6-sulfonamide; N-[4,5-dichloro-2-({[4-(3,5-dimethyl-1 H-pyrazol-1 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-methylthiophene-2 sulfonamide; 30 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 hydroxybenzoic acid; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-2 sulfonamide; 268 WO 2012/082633 PCT/US2011/064441 N-(4,5-d ichloro-2-{[(2,4-dichloro-5-methyl phenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-[4,5-dichloro-2-({[4-fluoro-3 (trifluoromethyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2-sulfonam ide; 5 methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoate; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxyth iophene-3-carboxylate; methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 furoate; 10 N-(4,5-dichloro-2-{[(2-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-1 H-pyrazole-3 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1-methyl-1 H-indole-7 15 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-pyridin-2-ylthiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(4'-fluorobiphenyl-4-yl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 20 N-(4,5-dichloro-2-{[(3-fluoro-4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3-dihydro-1,3 25 benzothiazole-6-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}furan-3-sulfonamide; N-[4,5-dichloro-2-({[3-(5-methyl-1,2,4-oxadiazol-3 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; ethyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-3-furoate; 30 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,4-dihydro-2H-1,5 benzodioxepine-7-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-1 -benzofuran-7 sulfonamide; 269 WO 2012/082633 PCT/US2011/064441 N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-2-methyl-1,3-benzothiazole-6 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-1,3,5-trimethyl-1 H-pyrazole-4 sulfonamide; 5 N-(4,5-dichloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-cyano-4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-1,3-thiazol-2 10 yl}acetamide; N-{4,5-d ichloro-2-[({4-[(6-methylpyrazin-2 yl)oxy]phenyl}sulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-(4,5-dichloro-2-{[(3-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 15 methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxybenzoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzothiophene-3 sulfonamide; N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-4-methyl-3,4-dihydro-2H 20 pyrido[3,2-b][1,4]oxazine-7-sulfonamide; 5-chloro-N-{4,5-dichloro-2-[(2-thienysulfonyl)amino]phenyl}-1,3-dimethyl-1 H pyrazole-4-sulfonamide; N-(4,5-dichloro-2-{[(5-chloro-2-naphthyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 25 N-{2-[(biphenyl-3-ylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide; N-(4,5-d ichloro-2-{[(2-fluoro-5-methyl phenyl)sulfonyl]am ino}phenyl)th iophene-2 sulfonamide; 4-chloro-3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 30 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxybenzoic acid; N-[4,5-dichloro-2-({[4-(pyridin-2-yloxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-naphthylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; 270 WO 2012/082633 PCT/US2011/064441 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; N-[4,5-dichloro-2-({[6-(d imethylam ino)-2-naphthyl]sulfonyl}am ino)phenyl]th iophene 2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; 5 N-(4,5-dichloro-2-{[(4'-chlorobiphenyl-4-yl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(2-{[(3-acetylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dioxo-1,2,3,4 tetrahydroquinoxaline-6-sulfonamide; 10 N-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzyl}acetamide; N-[4,5-dichloro-2-({[3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-[4,5-dichloro-2-({[2-(methylsulfonyl)phenyl]sulfonyl}am ino)phenyl]th iophene-2 15 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3-methylquinoline-8 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2,3-dihydro-1,4-benzodioxine-6 sulfonamide; 20 N-[4,5-dichloro-2-({[3-(2-methylpyrimidin-4 yl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 6-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}pyridine-3-sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-6-methoxypyridine-3 sulfonamide; 25 methyl 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methylbenzoate; N-(4,5-dichloro-2-{[(2,5-dimethoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(2-{[(4-acetylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2-sulfonamide; 30 methyl 3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2 methylbenzoate; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-isoxazol-5-ylthiophene-2 sulfonamide; 271 WO 2012/082633 PCT/US2011/064441 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-5-(1,3-oxazol-5-yl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(5-chloro-2-methylphenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; 5 N-[4,5-dichloro-2-({[5-(dimethylamino)-1 -naphthyl]sulfonyl}amino)phenyl]thiophene 2-sulfonamide; methyl 2-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methoxybenzoate; 5-chloro-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}thiophene-2 10 sulfonamide; N-(4,5-dichloro-2-{[(4-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-d ichloro-2-[(methylsulfonyl)am ino]phenyl}th iophene-2-sulfonamide; N-(4,5-dichloro-2-{[(3,5-dichloro-4-hydroxyphenyl)sulfonyl]amino}phenyl)thiophene 15 2-sulfonamide; N-[4,5-dichloro-2-({[4-chloro-3 (trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2-sulfonamide; 2-chloro-5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]benzoic acid; 20 N-[4,5-dichloro-2-({[4-(pyridin-3-yloxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-imidazole-4 sulfonamide; N-{4,5-d ichloro-2-[(ethylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; 25 N-(4,5-dichloro-2-{[(4-chloro-2-fluoro-5 methylphenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; 5-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-2-fluorobenzoic acid; N-{2-[(biphenyl-2-ylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide; 30 N-{3-[({4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}amino)sulfonyl]-4 methylphenyl}acetamide; N-(2-{[(5-tert-butyl-2-methylphenyl)sulfonyl]amino}-4,5-dichlorophenyl)thiophene-2 sulfonamide; N-{2-[(benzylsulfonyl)amino]-4,5-dichlorophenyl}thiophene-2-sulfonamide 272 WO 2012/082633 PCT/US2011/064441 N-{4,5-d ichloro-2-[(isobutylsulfonyl)am ino]phenyl}th iophene-2-sulfonamide N-{4,5-d ichloro-2-[(2-th ienylsulfonyl)amino]phenyl}-2,2-d imethylchromane-6 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1,2-dimethyl-1 H-imidazole-4 5 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-2-oxo-2,3,4,5-tetrahydro-1 H-1 benzazepine-7-sulfonamide; N-(4,5-dichloro-2-{[(4-cyclohexylphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; 10 4-chloro-N-1 -- {4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}benzene-1,3 disulfonamide; N-(4,5-dichloro-2-{[(4-fluorophenyl)sulfonyl]amino}phenyl)thiophene-2-sulfonamide; N-{3-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenyl}acetamide; 15 N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -methyl-1 H-indole-4 sulfonamide; N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-4,5-d ichlorophenyl)th iophene-2 sulfonamide; N-(4,5-dichloro-2-{[(3-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)thiophene-2 20 sulfonamide; N-{4,5-dichloro-2-[(5,6,7,8-tetrahydronaphthalen-2 ylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; N-[4,5-dichloro-2-({[4-(2-chlorophenoxy)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; 25 N-(4,5-dichloro-2-{[(4-methoxyphenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-(4,5-d ichloro-2-{[(2-methylphenyl)sulfonyl]amino}phenyl)th iophene-2-sulfonamide; 2-{4-[({4,5-dichloro-2-[(2 thienylsulfonyl)amino]phenyl}amino)sulfonyl]phenoxy}acetamide; 30 N-(4,5-dichloro-2-{[(2,4-dichlorophenyl)sulfonyl]amino}phenyl)thiophene-2 sulfonamide; N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,5-dimethyl-1 -phenyl-1 H pyrazole-4-sulfonamide; 273 WO 2012/082633 PCT/US2011/064441 N-{4,5-dichloro-2-[(2-thienylsulfonyl)am ino]phenyl}-4-methyl-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; 2-chloro-N-{4,5-d ichloro-2-[(2-thienylsulfonyl)am ino]phenyl}pyrid ine-3-sulfonamide; 4-acetyl-N-{4,5-dichloro-2-[(2-thienylsulfonyl)amino]phenyl}-3,4-dihydro-2H- 1,4 5 benzoxazine-6-sulfonamide; N-(4,5-d ichloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)th iophene-2 sulfonamide; N-{5-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{4-chloro-2-[(2-thienylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 10 N-{5-chloro-2-[(methylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-imidazole-4 sulfonamide; N-{2-[(benzylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; 15 N-(5-chloro-2-{[(4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-(5-chloro-2-{[(3-chlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(4-chlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; N-{5-chloro-2-[(2-naphthylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-8-sulfonamide; 25 N-(5-chloro-2-{[(3,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,4-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(biphenyl-4-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; 30 N-[5-chloro-2-({[4-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 274 WO 2012/082633 PCT/US2011/064441 N-[5-chloro-2-({[4-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 5 N-{5-chloro-2-[(1 -naphthylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2-chlorophenyl)sulfonyl]am ino}phenyl)-1 -benzofuran-2-sulfonamide; N-[5-chloro-2-({[3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; N-(5-chloro-2-{[(3,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 15 N-(2-{[(4-tert-butylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[2-({[4-(benzyloxy)phenyl]sulfonyl}amino)-5-chlorophenyl]-1 -benzofuran-2 20 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3-benzodioxole-5 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,4-dimethyl-1,3-thiazole-5 sulfonamide; 25 N-[5-chloro-2-({[3-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 30 sulfonamide; N-{5-chloro-2-[(2-furylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzothien-3-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 sulfonamide; 275 WO 2012/082633 PCT/US2011/064441 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3-benzothiazole-6 sulfonamide; N-[5-chloro-2-({[3-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 5 N-(5-chloro-2-{[(2-fluorophenyl)sulfonyl]am ino}phenyl)-1 -benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2,5-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[2-(trifluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 10 N-(5-chloro-2-{[(5-chloro-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 15 chlorophenyl}amino)sulfonyl]thiophene-2-carboxylate; N-{5-chloro-2-[(ethylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethylisoxazole-4 sulfonamide; N-(5-chloro-2-{[(5-chloro-3-methyl-1 -benzothien-2-yl)sulfonyl]amino}phenyl)-1 20 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(2-chloro-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 25 N-{5-chloro-2-[(isobutylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2-chloro-4 fluorobenzoic acid; N-{5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methyl-1,3-thiazol-2-yl}acetamide; 30 N-(5-chloro-2-{[(2,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4-chloro-2,5-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 276 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(4-chloro-3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 H-1,2,4-triazole-5 sulfonamide; 5 3-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]phenyl}propanoic acid; methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-5 chlorothiophene-2-carboxylate; N-{2-[(1 -benzofuran-5-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 10 sulfonamide; N-{3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]phenyl}acetamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxoindoline-5 sulfonamide; 15 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethyl-1 H-pyrazole 4-sulfonamide; N-[5-chloro-2-({[4-(2-methylphenoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3-dihydro-1,3 20 benzoxazole-6-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloro-1,3-benzothiazole 6-sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 ethoxybenzoic acid; 25 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 fluorobenzoic acid; N-(5-chloro-2-{[(2,6-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}isoquinoline-5-sulfonamide; 30 N-(5-chloro-2-{[(2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 277 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(5-isoxazol-3-yl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]benzoic acid; 5 N-(5-chloro-2-{[(3,4-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]benzoic acid; N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 10 methylphenyl}acetamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloroquinoline-6 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-3-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5-chloroquinoline-8 15 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}quinoline-6-sulfonamide; N-(5-chloro-2-{[(2,4-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 20 methoxybenzoic acid; N-(5-chloro-2-{[(2,4-dimethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[2-({[3,5-bis(trifluoromethyl)phenyl]sulfonyl}amino)-5-chlorophenyl]-1 -benzofuran 2-sulfonamide; 25 N-(5-chloro-2-{[(5-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide N-(5-chloro-2-{[(2,3-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,6-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 30 sulfonamide; N-(5-chloro-2-{[(2,5-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -(phenylsulfonyl)-1 H pyrrole-3-sulfonamide; 278 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(2,6-dichlorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3-chloro-4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5 N-[5-chloro-2-({[2-(methylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2,5-dichloro-3-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 H-pyrazole-4 10 sulfonamide; N-{5-chloro-2-[(2,3-dihydro-1 H-inden-5-ylsulfonyl)amino]phenyl}-1 -benzofuran-2 sulfonamide; methyl 4-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]benzoate; 15 N-(5-chloro-2-{[(2,4,5-trifluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-dimethylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4-methoxy-3-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 20 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-1,2,3,4 tetrahydroquinoline-6-sulfonamide; N-(5-chloro-2-{[(5-{[(dimethylamino)carbonyl]amino}-2 ethoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2-sulfonamide; 25 N-(5-chloro-2-{[(2-ethoxy-5 {[(methylamino)carbonyl]amino}phenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(2-{[(4-acetylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2-sulfonamide; methyl 3-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4 30 chlorophenyl}amino)sulfonyl]benzoate; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3-dihydro-1,3 benzothiazole-6-sulfonamide; N-{5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-1,3 thiazol-2-yl}acetamide; 279 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(3-chloro-4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2H-chromene-6 sulfonamide; 5 N-(5-chloro-2-{[(5-chloro-2,4-difluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methoxyphenyl}acetamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-morpholin-4-ylpyridine-3 10 sulfonamide; methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxyth iophene-3-carboxylate; N-{5-chloro-2-[(3-furylsulfonyl)amino]phenyl}-1 -benzofuran-2-sulfonamide; N-{5-chloro-2-[({4-[(6-methylpyrazin-2-yl)oxy]phenyl}sulfonyl)amino]phenyl}-1 15 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-pyrazole-5 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-phenylpyridine-3 sulfonamide; 20 N-[5-chloro-2-({[4-(1 -methyl-1 H-pyrazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-chloroimidazo[2, 1 b][1,3]thiazole-5-sulfonamide; N-{5-chloro-2-[({3-[(6-methylpyrazin-2-yl)oxy]phenyl}sulfonyl)amino]phenyl}-1 25 benzofuran-2-sulfonamide; methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 furoate; N-[5-chloro-2-({[3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 30 N-(5-chloro-2-{[(3-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 1 -acetyl-N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}indoline-5 sulfonamide; 280 WO 2012/082633 PCT/US2011/064441 ethyl 3-[({2-[(l-benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl] ison icotinate; N-(5-chloro-2-{[(5-methyl-1 -benzothien-2-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5 N-[5-chloro-2-({[3-(l -methyl-1 H-pyrazol-5-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}chromane-6-sulfonamide; N-(5-chloro-2-{[(2-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 10 ethyl 5-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-3 furoate; methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxybenzoate; N-(5-chloro-2-{[(4-pyrimidin-2-ylphenyl)sulfonyl]amino}phenyl)-1-benzofuran-2 15 sulfonamide; N-[5-chloro-2-({[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-[5-chloro-2-({[2-chloro-4-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 20 N-(5-chloro-2-{[(2,5-dimethyl-3-furyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; methyl 5-[({2-[(1-benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-1 methyl-1 H-pyrrole-2-carboxylate; N-[5-chloro-2-({[4-(3,5-dimethyl-1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]-1 25 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(4-chloro-2-fluoro-5-methylphenyl)sulfonyl]amino}phenyl)-1 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-pyrazole-3 sulfonamide; 30 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,5-dimethyl-1 -phenyl-1 H pyrazole-4-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-3,4-dihydro-2H 1,4-benzoxazine-6-sulfonamide; 281 WO 2012/082633 PCT/US2011/064441 N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,4-dihydro-2H-1,5 benzodioxepine-7-sulfonamide; N-[5-chloro-2-({[3-(l -methyl-1 H-pyrazol-3-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; 5 N-{5-chloro-2-[(2,3-dihydro-1 -benzofuran-5-ylsulfonyl)amino]phenyl}-1 -benzofuran 2-sulfonamide; N-[5-chloro-2-({[4-(pyrrolidin-1 -ylsulfonyl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(5-methyl-2-furyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; N-(5-chloro-2-{[(5-methyl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-indole-7 sulfonamide; 15 N-{5-chloro-2-[(2,3-dihydro-1 -benzofuran-7-ylsulfonyl)amino]phenyl}-1 -benzofuran 2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,2-dimethylchromane-6 sulfonamide; N-[5-chloro-2-({[4-(2-methyl-1,3-thiazol-4-yl)phenyl]sulfonyl}amino)phenyl]-1 20 benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-2-phenyl-1 ,3 thiazole-5-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-phenoxypyridine-3 sulfonamide; 25 methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methyl-3-furoate; N-[5-chloro-2-({[4-(phenoxymethyl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 30 hydroxybenzoic acid; N-(5-chloro-2-{[(5-pyridin-2-yl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-methyl-1,3 benzothiazole-6-sulfonamide; 282 WO 2012/082633 PCT/US2011/064441 N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-methyl-3,4-dihydro-2H pyrido[3,2-b][1,4]oxazine-7-sulfonamide; N-{2-[(l -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1 -methyl-1 H-indole-4 sulfonamide; 5 N-(5-chloro-2-{[(5-phenyl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3-oxo-3,4-dihydro-2H-1,4 benzoxazine-6-sulfonamide; 10 N-(5-chloro-2-{[(4-phenoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(1 -benzothien-2-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4'-fluorobiphenyl-4-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 15 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,3,5-trimethyl-1 H pyrazole-4-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5-chloro-1,3-dimethyl-1 H pyrazole-4-sulfonamide; 20 2-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 chlorophenyl}amino)sulfonyl]phenoxy}acetamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylbenzoic acid; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 25 methylbenzoic acid; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2,4 dichlorobenzoic acid; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-5,6-dichloropyridine-3 sulfonamide; 30 N-(5-chloro-2-{[(2,4-dichloro-5-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran 2-sulfonamide; N-(5-chloro-2-{[(3-fluoro-4-methoxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 283 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(4-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(1 H-pyrazol-1 -yl)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; 5 N-(5-chloro-2-{[(2,5-dimethyl-3-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(difluoromethoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(2-fluoro-4-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 10 sulfonamide; N-[5-chloro-2-({[4-fluoro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-(5-chloro-2-{[(3-chloro-2-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 15 N-(5-chloro-2-{[(3-cyano-4-fluorophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(5-chloro-2-naphthyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{2-[(biphenyl-3-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; 20 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-chloropyridine-3 sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}pyridine-3-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,3-dihydro-1,4 benzodioxine-6-sulfonamide; 25 N-(5-chloro-2-{[(5-isoxazol-5-yl-2-thienyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(3,5-dichloro-4-hydroxyphenyl)sulfonyl]amino}phenyl)-1 -benzofuran 2-sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 30 fluorobenzoic acid; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-1,2-dimethyl-1 H-imidazole 4-sulfonamide; N-(2-{[(4-bromo-3-methylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 sulfonamide; 284 WO 2012/082633 PCT/US2011/064441 N-(5-chloro-2-{[(2-fluoro-5-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-(5-chloro-2-{[(4'-chlorobiphenyl-4-yl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5 N-[5-chloro-2-({[3-(2-methylpyrimidin-4-yl)phenyl]sulfonyl}amino)phenyl]-1 benzofuran-2-sulfonamide; N-[5-chloro-2-({[5-(1,3-oxazol-5-yl)-2-thienyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]-1 10 benzofuran-2-sulfonamide; N-{2-[(biphenyl-2-ylsulfonyl)amino]-5-chlorophenyl}-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2-oxo-2,3,4,5-tetrahydro 1 H-1 -benzazepine-7-sulfonamide; N-(5-chloro-2-{[(3-chloro-4-cyanophenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 15 sulfonamide; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 chlorobenzoic acid; N-(2-{[(3-acetylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2-sulfonamide; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-chloropyridine-3 20 sulfonamide; N-(5-chloro-2-{[(5-chloro-2-methylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 chlorobenzoic acid; 25 N-{3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methylphenyl}acetamide; N-(5-chloro-2-{[(4-cyclohexylphenyl)sulfonyl]amino}phenyl)-1 -benzofuran-2 sulfonamide; N-{5-chloro-2-[(5,6,7,8-tetrahydronaphthalen-2-ylsulfonyl)amino]phenyl}-1 30 benzofuran-2-sulfonamide; 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxybenzoic acid; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-2,3-dioxo-1,2,3,4 tetrahydroquinoxaline-6-sulfonamide; 285 WO 2012/082633 PCT/US2011/064441 N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-6-methoxypyridine-3 sulfonamide; 4-acetyl-N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3,4-dihydro-2H 1,4-benzoxazine-6-sulfonamide; 5 N-[5-chloro-2-({[5-(dimethylamino)-1 -naphthyl]sulfonyl}amino)phenyl]-1 -benzofuran 2-sulfonamide; N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 chlorophenyl}acetamide; N-[5-chloro-2-({[4-(pyridin-3-yloxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 10 sulfonamide; N-(2-{[(5-tert-butyl-2-methylphenyl)sulfonyl]amino}-5-chlorophenyl)-1 -benzofuran-2 sulfonamide; N-1 -- {2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-4-chlorobenzene-1,3 disulfonam ide; 15 N-[5-chloro-2-({[4-(2-chlorophenoxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-[5-chloro-2-({[4-(pyridin-2-yloxy)phenyl]sulfonyl}amino)phenyl]-1 -benzofuran-2 sulfonamide; N-{4-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4 20 chlorophenyl}amino)sulfonyl]benzyl}acetamide; methyl 5-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylbenzoate; methyl 2-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-4 methoxybenzoate; 25 methyl 3-[({2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}amino)sulfonyl]-2 methylbenzoate; N-{2-[(1 -benzofuran-2-ylsulfonyl)amino]-4-chlorophenyl}-3-methylquinoline-8 sulfonamide; N-[5-chloro-2-({[6-(dimethylamino)-2-naphthyl]sulfonyl}amino)phenyl]-1 -benzofuran 30 2-sulfonamide; N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; and N-[5-chloro-3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2 yl]thiophene-2-sulfonamide. 286 WO 2012/082633 PCT/US2011/064441
[12] 12. A method of treating a disorder associated with chemokine receptor modulation, which comprises administering to a mammal in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of at 5 least one compound of Formula I R 6 O=s=o R3R 15 NR1 R14 R2 R17 N O=s=O Formula I wherein: 10 R 1 is H or substituted or unsubstituted C1.6 alkyl; R 2 is H or substituted or unsubstituted C1.6 alkyl; R 3 is N or C-R ; R 4 is N or C-R ; R 5 is substituted or unsubstituted C1.6 alkyl, substituted or unsubstituted heterocycle, 15 substituted or unsubstituted C3.8 cycloalkyl, substituted or unsubstituted C3.8 cycloalkenyl or is substituted or unsubstituted C6-10 aryl; R 6 is 2-benzofuran, 2 -thienyl, 5-chloro-2-thienyl, 4,5-dichloro-2-thienyl, 4-chloro-3 methylphenyl, or 4-chloro-3-trifluoromethylphenyl; R 15 is N or C-R16; 20 R 17 is N or C-R18 R 7 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 9 , NR 1 0 R 11 or hydroxyl; R 8 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 12 , NR 13 R 1 4 or hydroxyl; 25 R 16 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 19 , NR 20 R 21 or hydroxyl; 287 WO 2012/082633 PCT/US2011/064441 R 18 is H, substituted or unsubstituted C1.6 alkyl, halogen, -OC1-3 alkyl, CN, C 2-6 alkenyl, C 2-6 alkynyl, C(O)R 22 , NR 2 3 R 24 or hydroxyl; R 9 is H or substituted or unsubstituted C1.6 alkyl; R 10 is H or substituted or unsubstituted C1.6 alkyl; 5 R" is H or substituted or unsubstituted C1.6 alkyl; R 12 is H or substituted or unsubstituted C1.6 alkyl R 13 is H or substituted or unsubstituted C1.6 alkyl; R 1 4 is H or substituted or unsubstituted C1.6 alkyl; R 1 9 is H or substituted or unsubstituted C1.6 alkyl; 10 R 20 is H or substituted or unsubstituted C1.6 alkyl; R 2 1 is H or substituted or unsubstituted C1.6 alkyl; R 22 is H or substituted or unsubstituted C1.6 alkyl; R 2 3 is H or substituted or unsubstituted C1.6 alkyl; R 24 is H or substituted or unsubstituted C1.6 alkyl; 15 and including compounds: N-[3-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)pyridin-2-yl]thiophene-2 sulfonamide; N-[2-({[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl}amino)phenyl]thiophene-2 sulfonamide; and 20 N-{4,5-dichloro-2-[(3-thienylsulfonyl)amino]phenyl}thiophene-2-sulfonamide; and with the provisos: a) R 6 is not the same as R5; 0 -S S N b) when R 5 is a substituted heterocycle then it is not C1-3 alkyl c). when R 6 is 2-thienyl then R 7 , R 8 , R 16 and R 18 are not all hydrogen in same 25 time; d). the compound is not of the following structures: 288 WO 2012/082633 PCT/US2011/064441 ci ci F 3 C HNP / / F Br / OMe CI S H / S-NH S-NH Ci 0 or 0
[13] 13. A method of claim 12, wherein the pharmaceutical composition is 5 administered to the mammal to treat ocular inflammatory diseases or skin inflammatory diseases.
[14] 14. The method of claim 13 wherein the mammal is a human. 289

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

JPH06135934A|1991-12-27|1994-05-17|Ishihara Sangyo Kaisha Ltd|Phospholipase a2 inhibitor, anti-inflammatory agent of anti-pancreatitic agent containing pyridine derivative or its salt|

---

US6423343B1|1998-01-23|2002-07-23|Usbiomaterials Corporation|Bioactive glass treatment of inflammation in skin conditions|

---

GB9924522D0|1999-10-15|1999-12-15|Arrow Therapeutics Ltd|Enzyme inhibitors|

---

TWI328007B|2002-01-16|2010-08-01|Astrazeneca Ab|Novel compounds|

---

NZ536504A|2002-05-24|2008-04-30|Millennium Pharm Inc|CCR9 inhibitors and methods of use thereof|

---

US7393873B2|2003-07-02|2008-07-01|Merck & Co., Inc.|Arylsulfonamide derivatives|

---

CN101068804A|2004-10-21|2007-11-07|特兰斯泰克制药公司|Bissulfonamide compounds as agonists of GalR1, compositions, and methods of use|

---

AU2005299771A1|2004-10-21|2006-05-04|High Point Pharmaceuticals, Llc|Bissulfonamide compounds as agonists of GalR1, compositions, and methods of use|

---

EP2474532A1|2005-01-14|2012-07-11|ChemoCentryx, Inc.|Heteroaryl sulfonamides and CCR2|

---

US7622583B2|2005-01-14|2009-11-24|Chemocentryx, Inc.|Heteroaryl sulfonamides and CCR2|

---

US7931909B2|2005-05-10|2011-04-26|Allergan, Inc.|Ocular therapy using alpha-2 adrenergic receptor compounds having enhanced anterior clearance rates|

---

GB0524786D0|2005-12-05|2006-01-11|Glaxo Group Ltd|Compounds|

---

US20100234364A1|2006-07-14|2010-09-16|Arindrajit Basak|Ccr2 inhibitors and methods of use thereof|HUE049728T2|2012-03-01|2020-10-28|Allergan Inc|Benzofuran-2-sulfonamide derivatives as chemokine receptor modulators|

---

GB201223308D0|2012-12-21|2013-02-06|Univ Sunderland|Enzyme inhibitors|

---

CN109749059A|2017-11-03|2019-05-14|华南协同创新研究院|A kind of condensed ring N-shaped polymer of main chain cyano-containing indone and its application|

法律状态:
2017-08-17| FGA| Letters patent sealed or granted (standard patent)|

优先权:

---

申请号 | 申请日 | 专利标题

---

US42394110P| true| 2010-12-16|2010-12-16||

---

US61/423,941||2010-12-16||

---

PCT/US2011/064441|WO2012082633A1|2010-12-16|2011-12-12|Novel 1,2- bis-sulfonamide derivatives as chemokine receptor modulators|

---