 Method for flavonoid derivatives synthesis
专利摘要:
Substituted flavonoid compounds of the formula (I): are disclosed. These compounds possess anticancer activity, in particular antipancreatic cancer activity, together with immunomodulatory activity. 公开号:SU1739846A3 申请号:SU894613889 申请日:1989-04-05 公开日:1992-06-07 发明作者:Брие Филипп；Бертелон Жан-Жак；КОЛЛОНЖ Франсуа 申请人:Лифа-Лионнэз Эндюстриель Фармасетик (Фирма)； IPC主号:
专利说明:
one activity against pancreatic cancer and immunomodulatory properties. The purpose is achieved in that according to the method for producing compounds of the formula I, a compound of the formula (Ii) where X, R4 and R2 are as defined, is reacted with arbitrary cyanide, for example tetraethylammonium cyanide or potassium cyanide, in an environment of an organic solvent, such as chloroform or dichloroethane, at a temperature of 20-120 ° C for 4-24 hours R2 P (III) X rl CN where X, R 1 and RJ have the indicated meanings, hydrolyzed with hydrochloric or sulfuric acid in an acetic acid-water mixture at boiling for 4–8 h. Example 1. 1-Oxo-3-phenyl-1H-naphtho (2,1-b) pyran-5-acetonitrile „ C2, H, 5G) g, mol.m. 311,344. A mixture of 8.2 g (0.0224 mol} 5 bromobutyl-3-phenyl - (1H) -aphtho (2,1-b) of piral-1, 4.9 g (0.031 mol) of tetraethyl ammonium cyanide in 250 ml of dichloroethane are stirred for 18 hours at room temperature, using water, the resulting solid product is filtered and dried, 6.9 g (98% yield) are obtained, mp 260 ° C. IR spectrum, 7039; 2160 and 2220. 1 Oxo-3-phenyl-1H-naphtho (2,1-b) pyran-5-acetic acid, cr (H «| 04, mol.m. 330.34 (compound 1), A mixture of 6.9 g (0.022 mol) of 1-oxo-3-phenyl (1H) -aphtho (2,1-b) pyran-5-acetonitrile, 50 ml of acetic acid, 50 ml of water and 50 ml of concentrated sulfuric acid boil t with back fridge. The mixture is then poured into water and cooled to form 39846. In this case, the solid is centrifuged, dried and recrystallized from acetic acid. Obtain 2.1 g (yield 28%), so pl. 291-2930. ( IR spectrum, cm; , (acid) 1700; -) Cr0 (pyrone) 1638. NMR spectrum (DMSO), ppm relative to, TMS: 4.03 (s, 2H); 7.1 (s, 1H). 7.3-8.3 (n, 9H); 12.5 (rbmenyuschiy- s, 1H). Calculated D: C, 76.35; H 4.27; About 19.37. 5 FoundD: C 78.85; H 4.01. By this technique, get the track. compounds. 4-Oxo-2-phenyl-4H-naphtho (2,3-b) pyran-1-acetic acid. 20 mol.m. 330.34 (compound 2) „ M.p. 276-288 C. IR spectrum, cm: (acid) 1720; (pyrone) 7610., NMR spectrum (LMSO), ppm relative to TMS: 4.4 (s, 2H); 6.97 (s, 1H); 7.2-8.5 (m, 9H); 8.62 (s, 1H); 12.5 (exchanging, 1H). Calculated D: C 76.39; H 4.27; ° 19.38. 30 Found: C 79.9; H 4.39. 4-Oxo-2-phenyl-4H-naphtho (1,2-b) pyran-10-acetic acid. Czt .04, mol. 330.34 (compound 3). 35 m.p. 259-2614. IR Spectrum, Vc.o (acid) 1710; (pyrone) 7630. NMR spectrum (DMSO) J, ppm relative to TMS: 4.45 (s, 2H); 6.9 (s, 1H); 40 7.3-8.3 (m, YUN); 12.2 (exchanging, 1H). Calculated D: C 76.39; And 4.27; About 19.38. 45 Found: C, 76.24; H 4.07. 3 Methoxy-4-oxo-2-phenyl-H- (1) - benzopyran-8-acetic acid. mol.m. 310,292 (compound 4). 50 m.p. 187-192 C. IR spectrum, (acid) 1720; QOO (pyrone) 1610. NMR spectrum (DMSO) 4 ppm with respect to TMS: 3.8 (s, 3N) ,: 4 (s, 2H); “7.4-8„ 3 (m, 8H); 11.9 (exchanging, 1H). Calculated D: C 69.67; H 4.55; About 23.78. Found: C 69.90; H 4.55. 5-Methoxy-oxo. -phenyl (1) - benzopyran-8-acetic acid. H1405, mol. 310.9 (Compound 5). M.p. . IR spectrum, (acid) 172Q; c o (pyrone) NMR spectrum (DMSOLO, ppm with respect to TMS: MS, 5H): 7.2 (s, 1H); 7.7-8.7 (m, 7H); 12.2 (exchanging, 1H). Calculated: C 69,67; H, 55; About 29.78. Found: C 69.50; H k, 57, 2- (2-Methoxyphenyl) - -oxo-H- (1) -benzopyran-8-acetic acid. mol.m. 310,292 (connect 6) o M.pl 203-205 ° co IR spectrum, cm: (acid) 1730; (pyrone). NMR spectrum (DMSO) Ј, prgo in relation to TMS: It (s, 7 (s, 1H); 7.1-8.1 (m, 7H); 12.8 (exchanged 1H). Calculated: C 69,67; H, 55; About 25.78 Found: C 69.72; H 1 |, 39. -Oxy-4-oxo-2-phenyl-H- (1) -ben zopyran-I-acetic acid. c (tHtt ° 3 m ° l-m- 296.66, (compound 8) mp. 233-238 C. M.p. 221-223 C. IR spectrum, VC-Q (acid) 1700; (pyR ° n) 1610. NMR spectrum (DMSO) Ј, ppm with respect to TMS: k (s, 2H); 7.3-8, (m, 8H); 9.6 (exchanged, 1H); 12.3 (exchanged, 1H). Calculated: C 68,92; H M8; About 27.00. Found: C 68.86; H A, 01. 5-Hydroxy-oxo-phenyl-H- (1H) -be-zopyran-8-acetic acid. From “NL0, mol. M. 296, 266, (connection some 8), so pl. 233-238 C. IR Spectrum: c. # (Acid) 1700; (pyrone) 1680. NMR spectrum (DMSO), ppm with respect to TMS: 3.8 (s, 2H); 6.8 (d, 1H); 7.1 (s, 1H); 7, -8.2 (m, 6K); 42.4 (exchanged, 1H). Calculated: C 68,92; H A, 08; About 27.00. Found: C 68.85; And /, 22. 7-hydroxy-A-oxo-2-phenyl- / H- (1) -ben zpyrane-8-acetic acid. mol.m. 2ChB, 66 (compound 9). 398W6 M.p. 227-238 ° C. IR spectrum: v (acid) 1700; ) p.0 (pyrone) 1630., NMR spectrum (DMSO), ppm relative to TMS: 3.8 (s, 2H) 6.8-8.2 (m, 8H); 10.8-11.1 (exchangeable, 2H) Calculated: C 68.9 -; H, 08; 9 27.00. 10 Found: C, 68.92; H 1.00. 2- (2-hydroxyphenyl) - i-oxo-H- (1) - benzopyran-8-acetic acid. Ct7Hi2 3, molol. 296.266 (compound 1 0). 15 m.p. 288-292 ° C. IR spectrum, cm: Usso (acid) 1700; (pyrone) 1640. NMR spectrum (LMSO) §, ppm with respect to TMS: C (s, 1H); 7 (s, 1H); 20 7.2-8.2 (m, 7H), 10, P-1., 9 (exchanged, 2H). Calculated: C 68.92; H, 08; O 27, OP. Found: C 68.75; H 3.88. 25 2- (3-hydroxyphenyl) - -oxo-H- (1) -benzopyran-8-acetic acid. .P5 mol.m., 296.266 (compound 11). T. pl. 259-288 & C. IR spectrum, C-Q (acid) 30 | 1720; with 0 (pyrone) 1630. NMR spectrum (DMSO), ppm with respect to TMS:, 1 (s, 2H); 7 (s, 1H); 7.1-8.2 (m, 7H) ,: 10 (exchanged, 1H); 12.8 (1H). 35 Calculated: C 68.92; H, 08; About 27.00. Found: C 68.91; H A, 21. 2- (4-hydroxyphenyl) -U-oxo-H- (1) - benzopyran-8-acetic acid. ® mo.m. 296.266 (compound 12). M.p. 261-268 ° C. IR spectrum, (acid) 1690, N) (pyrone) 162P. 45 NMR spectrum (DMSO) $, ppm with respect to TMS: 3.8 (s, 2H); 6.7-8 (m, 8H); 10.3 (exchanged, 1H); 12.2 (exchanged, 1H). Calculated: C 68,92; H 4.08; 50 0 27.00. Found: C 68.61; H, 20. 2- (3-Diethylaminoethoxyphenyl) -4-oxo-H-benzopyran-8-acetic acid hydrochloride. S5 C23H26ClNOj, mol.m. f31,903 (compound 13). M.p. 176-179QC. IR spectrum, at (acid) 1720; (pyrone). 717398468 NMR spectrum (LMSO) $, ppm relative to NMR spectrum () $, ppm no to TMS: 1, h (t, 3N); 3-h „6 (m, with respect to TMS: and (s, 2H), 7-9 (m, 11H, of which 1H is interchangeable), 7J (s, 1H); 7.2-8.1 (m, 6H); 13.2 (interchangeable, 1H). Calculated D: 63.96; H 6.07; C1 8.21; N 3.24; About 18.32. Found 3: C 63.69; H 5.88; C1 8.09; N 3.01. 2- (2-Aoxyphenyl) -h-oxo-hN- (1) - benzopyran-8-acetic acid C2 N1b. M. 372.38 (compound 1h). Mp 218-220 ° C. IR spectrum, (acid) 1680; (pyrone). NMR spectrum (LMSO) 8, ppm with respect to TMS: 3.8 (s, 2H): 6.8-8 (m, 13H); 12.6 (interchangeable, 1H). Calculated D: S 7h, 19; Nh, 33; 21, p8. Found: C, 73.88; N h, 56. 6 Fluoro-h-oxo-2-phenyl-hH- (1) -benzopyran-8-acetic acid. C ,, mol.m. 298.26 (compound 15). Mp 225-239 ° C. IR spectrum, (acid) 1720; (pyrone) 1bcho. NMR spectrum (LMSO) 8, ppm with respect to TMS: H-3 (m, 3N, of which 1H is replaceable); 7 (s, 1H); 7 (7H); 8, h (m, 1H). Calculated D: C 68, AO} H 3.72; F 6.37; About 21.46. FoundD With 68,42; H 3.92; F 6.28, 2- (2-ftBrphenyl) -h-oxo-H- (1H) - benzopyran-8-acetic acid „ C H "F04, mol.m. 298.26 (connection 40). 8H). Calculated D: C 67.49; H 3.72; F 6.37; About 24.46, Found: C 68,54; H 3.80; - F 6.33. 2- (3-fluorophenyl) -h-oxo-hH- (1) - JQ benzopyran-8-acetic acid. mol.m. 297.26 (compound 18) o T „pl„ 201-203 ° With IR spectrum, CM: VC “.O (acid), 5 1700; (pyrone). NMR spectrum (DMSO) and, ppm at fire to TMS: h (s, 2H); 7.1 (s, 1H); 7.2-8 (m, 7U; 12.6 (interchangeable, 1H) " 20 Calculated D: C 68.49; H 3.72; F 6.37; About 21.46. Found: C 68.20; H 3.69; F 6.28. 2- (h-Lenilphenyl) -h-oxo-hN- (1) - 25 benzopyran-8-acetic acid. C2.,) H (B04, mol.m. 356.36 (compound 19). M.p. 229-231 C. IR spectrum: v (acid) hell 17U; . (pyrone) 1620. NMR spectrum, (DMSO) tf, ppm with respect to TMS: h (s, 2H); 7 (s, 1H) 7.2-8 rh (m, 12H); 12.6 (interchangeable 1H). Calculated D: C 77.51; H 4.53; 35 About 17.96. Found: C, 77.42; H 4.41. 2- (h-Chlorophenyl) -h-oxo-hN- (1) -ben zopyran-8-acetic acid, mol.m. 31h, 71 (compound 16) M.p. 193-199 ° C. . IR spectrum, with a ". O (acid) 1720; (pyrone) 1610. NMR spectrum (LMSO) &, ppm with respect to TMS: h (s, 2H); 6.7 (s, 1H); 7.2-8, h- (m, 7H); 12.5 (interchangeable 1H). Calculated D: C 68.49; H 3S72; F 6.37; About 21.46. Found: C 68.42; H 3.92; F 6.28, 2- (h-Ltorphenyl) -h-oxo-hN- (1) -benzopyran-8-acetic acid " G 7HHFO, mol.m., 298.26 (compound 17). M.p. 215-217 ° C. IR spectrum,: V С00 (acid) g 1720; with “o (pyrone) 1bcho. M.p. 238-2h2 S. IR spectrum, (acid) 1720; ea (pyrone) 1620. 45 NMR spectrum (LMSO), ppm with respect to TMS: h (s, 2H); 7 (s, 1H) 792-8.2 (m, 7H); 12.5 (interchangeable, 1H). Calculated D: C, 64.87; H 3.52; 50 C1 11.27; About 20.34, Found D: C 64.83; H 3.37; C1 11.55. 2- (h-Carboxyphenyl) -h-oxo-hH- (1) benzopyran-8-acetic acid. 55 t8Htl ° mol m 32 h, 2 (compound 21). M.p. 312-314 S. IR spectrum. us-0 (acid) 1700-1720 ,: (pyrone) 1bCO. with respect to TMS: and (s, 2H), 7-9 (m, 20). 8H). Calculated D: C 67.49; H 3.72; F 6.37; About 24.46, Found: C 68,54; H 3.80; F 6.33. 2- (3-fluorophenyl) -h-oxo-hH- (1) - benzopyran-8-acetic acid. mol.m. 297.26 (compound 18) o T „pl„ 201-203 ° With IR spectrum, CM: VC “.O (acid) 1700; (pyrone). NMR spectrum (DMSO) and, ppm at fire to TMS: h (s, 2H); 7.1 (s, 1H); 7.2-8 (m, 7U; 12.6 (interchangeable, 1H) " Calculated D: C 68.49; H 3.72; F 6.37; About 21.46. Found: C 68.20; H 3.69; F 6.28. 2- (h-Lenilphenyl) -h-oxo-hN- (1) - benzopyran-8-acetic acid. C2.,) H (B04, mol.m. 356.36 (compound 19). M.p. 229-231 C. IR spectrum: v (acid) 17U; . (pyrone) 1620. NMR spectrum, (DMSO) tf, ppm with respect to TMS: h (s, 2H); 7 (s, 1H); 7.2-8HP (m, 12H); 12.6 (interchangeable 1H). Calculated D: C 77.51; H 4.53; About 17.96. Found: C, 77.42; H 4.41. 2- (h-Chlorophenyl) -h-oxo-hN- (1) -benzopyran-8-acetic acid, , mol.m., 31h, 71 (compound 20). M.p. 238-2h2 S. IR spectrum, (acid) 1720; ea (pyrone) 1620. NMR spectrum (LMSO), ppm relative to TMS: h (s, 2H); 7 (s, 1H); 792-8.2 (m, 7H); 12.5 (interchangeable, 1H). Calculated D: C, 64.87; H 3.52; C1 11.27; About 20.34, Found D: C 64.83; H 3.37; C1 11.55. 2- (h-Carboxyphenyl) -h-oxo-hN- (1) benzopyran-8-acetic acid. t8Htl ° "mol" m 32h, 2 (compound 21). M.p. 312-314 S. IR spectrum. us-0 (acid) 1700-1720 ,: (pyrone) 1bcho./ Calculated,%: C, 66.67; H 3.73; About 29.69. Found D: C 66.76; H 3.73. 4- (2-torphenylphenyl) -4-oxo-4I- (1) -benzopyran-8-acetic acid. mol.m. 374.35 (comp. 22). M.p. 22b-228 S. IR spectrum: v (acid) 1720;} s 0 (pyrone) 1630. NMR spectrum (LMSO) 8, ppm with respect to TMS: k (s, 2H); , 4 (m, 12H); 12.8 (exchanged, 1H). Calculated D: C 73.79; H 4.04; F 5.08; About 17.01, Found: C 73.80; H 4.14; F 4.87, 2- (2-Nitrophenyl) -4-oxo-4H- (1) - benzopyran-8-acetic acid. With ,, mol.m. 325.28 (compound 23), M.p. 180-182 ° C, IR spectrum, cm PC (acid) 1700; } Sw0 (pyrone) 1640. NMR spectrum (DMSO) Ј, ppm with respect to TMS: C (s, 2H); 6.8 (s, 1H); 7.3-8.3 (m, 7H; 12.8 (exchanged, 1H). Calculated D: C, 62.77; H 3.41; 4.31; about 29.51. Found,%: C 62.82; H 3.47; N 4.20. 2- (3-Nitrophenyl) -4-OXO-4H- (1) - benzopyran-8-acetic acid, С 7НЦШб, МОЛОМо 325.28 (compound 24). M.p. 203-2084, IR spectrum, V (acid) 1700; (pyrone) 1630. NMR spectrum (DMSO) $, ppm with respect to TMS: k (s, 2H); 7.3 (s, 1H); 7, -9 (m, 7H); 12.6 (exchanged, 1H). Calculated,%: C, 62.77; H 3.41; N 4.31; About 29.51 ,, Found,%: C 62.49; H 3.40; N 4.31. 2- (4-Nitrophenyl) - -oxo-H- (1) - benzopyran-8-acetic acid, C 7HMN06, mol.m. 325.28 (compound 25). „ M.p. . IR spectrum, cm (: V (acid) 1720; (pyrone) 1620. NMR spectrum (LMSO), ppm with respect to TMCi A (s, 2H); 7 (s, 1H); 7.2-8.3 (m, 7U;; 5 (exchanged, 1H). Calculated D: C, 62.77; H 3.1; N 4.31; p 29.51. Found,%: C 62.92; H 3.38; N 4.28. 2- (3-Aminophenyl) -4-OXO-4H- (1) is benzopyran-8-acetic acid. CtTHf3N04, mol.m. 295.28 (compound 26) 0 M.p. 227-239 ° C, IR spectrum, V (acid) 1720; N) (pyrone) 1630. NMR spectrum (DMSO) §, ppm with respect to TMS: 4 (s, 1H); 6.8-8 (m, 5 9H); 12.6 (interchangeable, 1H). Calculated D: C 69,14; H 4.44; N 4.74; About 21.67. Found: C, 69.20; H 4.70; N 4.94 „ 2- (4-Aminophenyl) -4-oxo-4H- (1) is benzopyran-8-acetic acid. . mol.m0 295.28 (connection 27). Mp, 189 ° C. J IR spectrum, cm (acid) 1700; C: i0 (pyrone) 1620. Calculated D: C 69,14; H 4.44; N 4.74; About 21.67, Found: C 69.00; H 4.48; N 4.66, 4-Oxo-2-phenyl-4H- (1) -benzopyran-8-acetic acid. ., mol. 280.28 (compound 28). M.p. .40-242 ° C. 5 IR spectrum, (acid) 740; Vc 0 (pyrone) 164P. NMR spectrum (LMSO) O, ppm with respect to TMS: 4 (s, 2H): 7 (s, 1H); 7.2-8.4 (m, OH); 12.6 (interchangeable, 0 1H). Calculated D: C, 72.85; H 4.32; - O 22.83, Found: C 73.00; H 4.16. 4-Oxo-2-phenyl-4H- (1) -benzopyran-7-acetic acid. C 0-4 mol.m. about 280.28 (compound 29). M.p. 237-239 ° С „ IR spectrum, cm (: y (acid) 1740; s-o (pyrone) 1620, NMR spectrum (LMSO) $, ppm with respect to TMS: 3.7 (s, 2H); 6.8 (s, 5 1H); 7.2-8 (m, 7H); 12.5 (ee replacement, 1 N). Calculated D: C, 72.85; H 4.32; About 22.83, Found: C, 72.73; H 4.33, 11173984612 2-Trifluoromethyl-4-oxo-4H- (1) -ben - T „pl„ 182-184 ° C. zopyran-8-acetic acid. iIK-spectrum, cm (: (acid) 1700; (pyrone) 1600. NMR spectrum (LMSO) 8, ppm with respect to TMS: k (s, 2H); 7.4-8.6 (m, 8H); 12.5 (interchangeable, 1H) 0 Calculated D: C 59.49; H 3.52; O 13.98; Se 23.00. Found: C 59.30; H 3.26; C17.H7F9 ° 4 mol ° m-, 17 (compound 30). Mp: 141-143 ° C. IR spectrum, (acid) 1700; (pyrone) 1650. Calculated,%: C, 52.95; H 2.59; F 20.94; About 23.52. Found: C, 52.72; H 2.64; F 20.35, 4-Oxo-2-phenyl-4H- (1) -benzothiopira-8-acetic acid. C17H, Z03S, mol.m. 296.34 (compound 31). m.p. 198-2PO ° s. IR spectrum, (acid) 1720; (pyrone) 1610. ten 15 Se 22.91. 7-Oxo-7H-benzo (c) xantenyl-11-acetic acid. , GL4, mol.m ,, 304.31 (compound 35). M.p. 270-272 C. IR Spectrum, VCtO (acid) 1720; VCeQ (pyrone) 1620. NMR spectrum (DMSO) Ј, ppm by otv, g- -. L - - f and - - / u f f NMR spectrum ((LMSO) 0, ppm relative to w TMS: 4 (s, 2H); 7, -9.2 to TMS: k (s, 2H); 7.3 (s, 1H); 7.3-8, (m, 7H); 12.5 (interchangeable, 1H). Calculated D: C 68.40; H 4.08; About 16.20; S 10.82. Found: C 69.04; H 4.29; S 11.04. A-Oxo-2-phenyl-H- (1) -beneothiopyran-8-acetic acid. C, 7H ,, mol.m. 328.3 (compound 32). M.p. W-187 ° C. . IR spectrum, (acid) 1700; (pyrone) 1660. NMR spectrum (LMSO) 8, ppm with respect to TMS: b (s, 2H); 7 (s, 1H); 35 0 18.06 (m, 9H); 12.5 (interchangeable, 1H). Calculated D: C 74.99; H 3.97; About 21.03 Found: C, 74.34; H 3.93. 25 4-Oxo-7-7H-dibenzo (s, p) xantenyl-1-acetic acid. CgNH14p4 mol.m. 35.37 (compound 36). M.p. 276-278 ° C. IR Spectrum, VC-Q (acid) 30 1700; (pyrone) 1620. NMR spectrum (LMSO) o, ppm with respect to TMS: 4 (s, 2H); 7, -8.8 (m, 11H); 12.5 (interchangeable, 1H). Calculated D: C 77.96; H 3.98; 7.2-8.2 (m, 7H) {12.6 (replaceable, H). Calculated D: C 62,18; H 3.68; O 24.36; S 9.77 Found: C, 62.29; H 3.68; S 9.65. -Oxo-2-phenyl-1, -dihydroquinoline-8-acetic acid. mol.m. 279.29 (compound 33). M.p. 236-2384. IR spectrum, cm: V (acid) 1680; (pyrone) 1620. NMR spectrum TPM (LMSO), ppm with respect to TMS (s, 2H); 7-8.3 (m, 50 ny 38) Found: C 77.94; H 3.97. 2- (A-Carboxymethylphenyl) (1) - benzopyranon-Av С17н1г ° 4 mol.m. 280.17 (comp. 37). M.p. IR spectrum, cm: US-o (acid) 1720; (pyrone). Calculated D: C, 72.84; H 4.32; 45 O 22.84 „ Found: C, 72.08; H 4.33. 2- (3-Carboxymethylphenyl) (1) - benzopyranone-A. , g ° 4 mol.m., 280.27 (co-8H); 8.5 (interchangeable, 1H). Calculated D: C 73.11; H 4.69; N 5.01; About 17.18. Found,%: C 73.10; H 4.62; N 5.04. 4-Oxo-2-phenyl-4H- (1) -benzoseleno-pyran-8-acetic acid. mol.m. , 24 (compound 3). M.p. 181-183 ° C. IR spectrum, (acid) 1720; with o (pyrone) 1620. NMR spectrum (LMSO) Ј, ppm with respect to TMS: 3.8 (s, 2H); 7 (s, 1H); 7, -8.2 (m, 8H); 12.4 (interchangeable, 1H). Calculated D: C, 72.84; H 4.32; About 22.84. Found: C 59.30; H 3.26; Se 22.91. 7-Oxo-7H-benzo (c) xantenyl-11-acetic acid. , GL4, mol.m ,, 304,31 (compound 35). M.p. 270-272 C. IR Spectrum, VCtO (acid) 1720; VCeQ (pyrone) 1620. NMR spectrum (DMSO), ppm by - f and - - / u f f wearing TMS: 4 (s, 2H); 7, -9.2 wearing TMS: 4 (s, 2H); 7, -9.2 0 18.06 (m, 9H); 12.5 (interchangeable, 1H). Calculated D: C 74.99; H 3.97; About 21.03 Found: C, 74.34; H 3.93. 4-Oxo-7-7H-dibenzo (s, n) xanthenyl-1-acetic acid. CgNH14p4 mol.m. 35.37 (compound 36). M.p. 276-278 ° C. IR Spectrum, VC-Q (acid) 1700; (pyrone) 1620. NMR spectrum (LMSO) o, ppm with respect to TMS: 4 (s, 2H); 7, -8.8 (m, 11H); 12.5 (interchangeable, 1H). Calculated D: C 77.96; H 3.98; position 38) Found: C 77.94; H 3.97. 2- (A-Carboxymethylphenyl) (1) - benzopyranon-Av С17н1г ° 4 mol.m. 280.17 (compound 37). M.p. IR spectrum, cm: US-o (acid) 1720; (pyrone). Calculated D: C, 72.84; H 4.32; About 22.84 „ Found: C, 72.08; H 4.33. 2- (3-Carboxymethylphenyl) (1) - benzopyranone-A. , g ° 4 mol.m., 280.27 (compound 38) M.p. 181-183 ° C. IR spectrum, (acid) 1720; with o (pyrone) 1620. NMR spectrum (LMSO), ppm in relation to TMS: 3.8 (s, 2H); 7 (s, 1H); 7, -8.2 (m, 8H); 12.4 (interchangeable, 1H). Calculated D: C, 72.84; H 4.32; About 22.84. 13 Found: C 73.08; H 4.41. 2 - (.- Carboxymethylphenyl) -4H- (1) - benzolyranone-4. m ° l „m 280.27 (compound 39) .0 M.p. 179-181 C. IR spectrum, V s-o (acid) 1730; } (pyrone) 1630. NMR spectrum (LMSP) J, ppm with respect to TMS: 3.9 (s, 2H); 6.6 (s, 1H); 7.2-8.2 (m, 8H); 12, C (replaceable ,, 1H). Calculated D: C, 72.84; H 4.32; About 22.84. Found: C 73.79; H 4.34 „ L 4-Oxo-3-Phenyl-4H- (1) -benzopyran-8-yl} methyl | phosphonate diethyl ether. C2oH2 ° sP mol.m. 372.39 (compound 4o) „ M.p. 107-109 ° C. IR spectrum, (pyrone) 1640. NMR spectrum (CDC13) Ј, ppm with respect to TMS: 1.2 (d, 61 $ 3.57 (d, 2H); 3.7-4.4 (m, 4H); 6.85 (s, 1H); 7.2-8, C (m, 8H). Calculated D: C 64,51; H 5.69; About 21.48; R 8.32. Found: C 64,59; H 5.67; P 8.17. Ј 4-Oxo-2-phenyl-4H- (1) -benzopyl ran-8-yl methyl phosphonic acid. C16H, aOЈ, mol. Mo 316.24 (compound 41). M.p. 331-334 ° C. IR spectrum, cm: 3on 3200-2200; (pyrone) 1620. NMR spectrum (DMSO) ft, ppm relative to TMS; 3.45 (d, 2H); 7.03 (s, 1H); 7.2-8.4 (m, 8H); 9.7 (replaceable, 2H) " Calculated D: C 60,76; H 4.14; O 29.30; R 9.80, Found: C 60,77; H 4.17; R 9.83. Example 2. 2--2-Phenyl-4-oxy-so-4H- (1) -benzopyran-8-pc acrylic acid, CteHis-Ojj, mol ° m - 292.27 (compound 42). 8.4 g (0.03 mol) of 4-oxo-2-phenyl-4H- (4) -benzopyran-8-acetic acid and 81 ml of N, N, N, N - tetramethyldiaminomethane are mixed. Then, 81 ml of acetic acid is added to the reaction mixture, cooled on a cold bath. Raise the temperature to 65 ° C, then lower it to 20 C. Continue stirring for 398461A 1 h, then the mixture is poured into water. The resulting solid is centrifuged, dried and recrystallized. Called from acetic acid. 3.4 g of product are obtained (yield 38.6%) m.p. 240-247 ° С „ IR spectrum, US-O (acid) 1689; (pyrone) 1620G 10 NMR spectrum (DMSO) Q, rrtp in relation to TMS: 6.3 (l, 2I); 7 (s, 1H); 7.3-8.2 (m, 8H); 13 (replaceable, 1H). Calculated D: 73.96; H 4.14; About 21.90. 5 FoundD: C 74.21: H 4.15, Example 3 3-enyl-2-2-phenyl-4-oxo-4H- (1) -benzopyran-8-yl brilic acid. mol.m. 368.36 (Compound 43). A mixture of 9.2 g (0, OR-7 mol) benzaldehyde, 16.8 g (0, V mol) 4-oxo-2-phenyl-4H- (1) -benzopyranoacetic acid, 30.9 ml acetic anhydride and 25 8.32 ml of triethylamine are boiled under reflux for 10 minutes. The mixture is then poured into 30 ml of water. The precipitate formed is centrifuged, dried and recrystallized from 30 acetic acid. 9.8 g of product are obtained (yield 44.3%), m.p. 215-220 ° C. IR spectrum, cm: V (acid) 1680; ) s-0 (pyrone) 1630. NMR spectrum (DMSO) o, ppm with respect to TMS: 6.8 (m, 15H), 12.5 (replaceable). Calculated D: C 78.25; H 4.39; About 17.31. Found: C, 77.90; H 4.11. 0 According to this procedure, the following compounds are obtained. 3- (2-Bromophenyl) -3-G2-phenyl-4-ox-4H- (1) benzopyran-o-yl Tacrylic acid, 45., They say. 447.27 (compound 44). M.p. 217-219 ° С „IR spectrum,: y (acid) 1680; (pyrone) 1640. 50 NMR spectrum (DMSO) Q, ppm with respect to TMS: 6.8-8.1 (m, 14H), 12.8 (interchangeable, 1H). Calculated D: C 64.44, H 3 # 38; Br 17.87; About 14.31. 55 Found: C, 64.29; H 3.37; Вг 17,58. 3- (4-Pyridinyl) -3-2-phenyl-4-ox-with-4H- (1) -benzopyran-8-yl acrylic acid. 15 . ., MOL.M ,, 369.36 (compound 5). M.p. 272-283 ° C, IR spectrum, (acid) 1700; N) (pyrone) 1640. NMR spectrum Л LMSO СО, pptn with respect to TMS: 6.8-8, 4 (m, 14H); 12.8 (replaceable, 1H} „ Calculated: C 74.69; H 4.09; And 3.79; About 17.33 Found: C, 74.54; H 4.00; N 3.79, 3- (3-Pyridyl) -2-phenyl-4-oxo-4H- (1) benzopyrana and kryl acid. C23H1S N04 mol "m ° 369.36 (compound 46)„ M.p. 118-124 S. IR spectrum, cm: v (acid) 1720; (pyrone) 1630. NMR spectrum, (LMSO), ppm in relation to TMS: 7-I, 5 (m, 14H),: 12, (replaceable). Calculated D: C, 74.79; H 4.09; N 3.79; About 17.33 Found,%: C 74.36; H 4.09; N 3.50. EXAMPLE 4 Chlorohydrate of 8- (4-methylpiperazinyl) methyl -2-phenyl-4H- (1) -benzopyranone-4. C2, NgzS1M202, mol.m. 370.87 (compound 47) " 18.9 g (O, O6 mol) of 8-bromomethyl-4-ca-2-phenyl-4H- (1) -benzopyranone, 6.57 g (0.066 mol) of N-methyl piperazine and 8.3 g (0.06 mol) of potassium carbonate with 200 ml of toluene for 8 hours. Insoluble products are filtered off and the solvent is evaporated off under vacuum. The resulting solid was recrystallized from hexa. 9.69 g of product are obtained, m.p. 139 ° C. IR spectrum, cm. N (pyrone) 161.0. ° After treatment with HC1 in CHCl, hydrochloride is obtained with ToPl,. Calculated,%: C 68.00; H 6.25; C1 9.56; N 7.56; About 8.63. Found,%: C 68.34; H 5.86; C1 9.80; N 7.61. By this procedure, the following compounds are prepared. P 1 Bromhydrate No.- (imidazolyl 2) -№- С-oxo-2-phenyl-H- (1) benzopyranyl or methyl} -2,6-dichloraniline. S25.NyVgSNH5Og, mol.m. 26 (compound 48). , M.p. 289-290 ° C. , IR spectrum: (pyrone) -) cc 3000-3200. NMR spectrum (LMSO), ppm with respect to TMS: 3, C (s, H); 5.5 (s, 2H); 7 (s, 1H); 7.2-8.3 (m, 11H); 8.5-9.5 (interchangeable with 2H). Calculated 3: C 55.06; H 3.70; Br 14.66; C1 13.00; N 7.71; Yu About 5.87. Found,%: C 55.14; H 3.63; Br 14 56; C1 13.09; N. } - {-Oxo-2-phenyl-H- (1) -benzopyran-8-yl methylamino | benzoic acid - 15 lots. mol.m. 371,396 (compound 9). M.p. 2b9-271 ° C. IR spectrum,: Y (acid) 1710; } Сш0 (pyrone) NMR spectrum (LMSO), ppm with respect to TMS:, 8 (m, 2H); 6.9-8.27 (m, 13H); 12.6 (interchangeable, 1H). Calculated: C 74.38; H 4.61; 25 N 3.77; About 17.24. Found 3: C, 74.08; H 4.59; N 3.91 o g 4-N-JC -Oxo-2-phenyl-H- (1) -ben-4Zopyran-8-ylD methyl 1-M-methylaminoben-3Q soyric acid. Szdntko, mol.m. 385.2 (compound 50), M.p. 260-262 ° C. IR spectrum, (acid) 1710; (pyrone) 16AO. 35 NMR spectrum (DMSO) tf, ppm relative to TMS: 3.2 (s, 3N); 5 (s, 2H); 6.8-8.4 (m, 13H); 12.6 (interchangeable 1H). Calculated D: C, 74.79; H 4.97; w N 3,63; About 16.60. Found: C, 74.51; H 4.81; N 3.47. 3- {C 1 -Oxo-2-phenyl-4H- (1) -benzopyran-8-yl methylamine} -3-methylpropandiol-1,3. С2онЈ4ш4 339,398 (compound 5i. M.p. 150-152 C. 50 IR spectrum, (pyrone) 1630; } Oi 3380. NMR spectrum (LMSO) d, ppm with respect to TMS: 1 (s, 3N); 3.2 (d, 4H); k (s, 2H); 4.5 (t, replaceable, 55 2H); 7 (s, 1H); 7.2-8.2 (m, 8n). Calculated D: C, 70.78; H 6.24; N 4.13; About 18.25. Found: C 70,5t; H 6.42; N 4.37. 17 8- (Aminomethyl) -2-phenyl-4H- (1) -benzopyranone-40 hydrochloride C16H |, C1Sh4, mole, m „287.19 (compound 52). M.p. 275-279 ° C. IR spectrum: V MCs ", (+) ZUO- 2600; -) (pyrone) 1620. NMR spectrum (DMSO) 8, ppm with respect to TMS: 7.3-8.4 (m, 8H); 8.8 (interchangeable, RN) Calculated: C 64,76; H 5.1; C1 11.95; N A, 72; About 13.48. Found: C 65.05; H 4.73; C1 12.08; N 4.46 „ 2-benil-8- (3,4, 5-trimethoxyphenyl aminomethyl) -4H- (1) -benzopyranon-4 ", C HzaNOg-, mol0m „417.47 (compound 53). M.p. 219-222 C. IR spectrum, Hc, and 3350; Vc.0 (pyrone) 1620, NMR spectrum (CFCOOD3) b, ppm with respect to TMS: 3.15 (s, 6H) 5 3.35 (s, 3N); 4.93 (s, 2H); 6.1 (s, 1H); 7-8.3 (m, 11H). Calculated: C 74.93; H 5.55; N 3.35; About 19.16, Found: C 71.65; H 5.58; N 3.35 „ PRI me R 5. 8- (1-Acetyloxyethyl) -2-phenyl-4H- (1) -benzopyranon-4 mol.m. 308.32 (compound 5h) o 6.2 g (0.186 mol) of 8- (1-bromoethyl) -2-phenyl-4H- (1) -benzo-pyranone-4 and 20.1 g (0.204 mol) of potassium acetate in 290 ml of DM and heat are mixed. stirring to 45 ° C., heating is stopped and the reaction mixture is cooled to room temperature for 3 hours at. stirring. After standing overnight, the mixture is poured onto ice. The precipitate formed is filtered off and recrystallized from alcohol. 51 g of product are obtained (yield 88.9%), mp. 137 ° C. IR spectrum: V (ester) 1740; ) (pyrone) 1640. NMR spectrum (CDCl 3) Ј, ppm with respect to TMS: 1.7 (d, 3N); 2.1 (s, 3N); 6.6 (d, 1H); 6.8 (1H); 7.2-8, k (m, 3N). Example 6 “8- (1-Hydroxyethyl) -2-phenyl-H- (1) -benzopyranone-. spnn ° z "m-m. 266.3 (Compound 55). T9.3 g (0.63 mol) of 8- (1-acetyloxyethyl) -2-phenyl-4H- (1) to are mixed. 15 benzopyranone-, 68.8 g (0.818 mol) of sodium bicarbonate in 239 ml of ethanol and 1628 ml of water. The mixture is boiled under reflux, the filtrate is evaporated in vacuo, the residue is treated with water and recrystallized from toluene. Obtain 152.9 g of product (yield 91%), so pl. 15 -1571} S. IR spectrum, cm (3350; Vc..0 (pyrone) 1620. NMR spectrum (CDCl1) o, ppm with respect to TMS: 1.62 (d, 3N); 2.8 (interchangeable, 1H). Calculated: C 76.67; H 5.30; About 18.03. Found: C 76.50; H 5.19. Example. 8-Acetyl-2-phenyl-H- (1) -benzopyranone-4th C17H12pe mol „m. 26A, 28 (compound 56). 59.5 g of (P, 223 mol) of 8- (1-hydroxyethyl) -2-phenyl-H- (1) -benzopyranone are placed in 670 ml of dioxane. The mixture, g, is heated until solution is obtained. Then it is cooled to 20 ° C and a reagent solution prepared from 19.7 g (0.19 mol) of CrO, 50 ml of water and 13.6 ml of concentrated sulfuric acid are added dropwise. This mixture is kept at room temperature with stirring, the insoluble products are filtered off, the filtrate is removed. evaporated in vacuo and the resulting residue is recrystallized from methyl- 35 isobutyl ketone. 43.3 g of product are obtained (yield 73.4), Top. 125-12b ° C. IR Spectrum, (ketone) 1675; (pyrone) 1640. NMR spectrum (CDCl 3) O, ppm relative to 40 TMS: 2.8 (s, 3N); 6.8 (s, 1H); 7.3-8.6 (m, 8H). Calculated: C 77.26; H 4.58; About 18.16 „ Found: C, 77.23; H 4.53 „45 EXAMPLE 8. 8- (Bromoacetyl) -2-phenyl-H- (1) -benzopyranon-A. , they say „m. , 18 (compound 57) o To a solution of 40 g (0.19 mol) of 8-50 acetyl-2-phenyl-4H- (1) -benzopyranone-4 in 50 ml of dioxane was added 56.9 g (0.151 mol) of phenyltriethylammonium tri-bromide. The mixture is stirred for 48 hours at room temperature, filtered and 55 the resulting precipitate is washed with water and recrystallized from acetone. 42.9 g of product are obtained (yield 82), m.p. 142 ° C. IR spectrum. cm: at 1630. 191739846ZO NMR spectrum (CDC1}) Ј, ppm relative to the IR spectrum, - from about 635. to TMC:, 6 (s, 2H); 6.8 (s, I 1H); 7.2-8.6 (n, 8H). LR mimep 9. 8- (2-Aminothiazol-i-yl) -2-phenyl-H- (G) -benzopyranon-A. C№H12N202S, mol. M, 320.37 (compound 58). A mixture of 5 g (0, mol) of 8- (bromo-acetyl) -2-phenyl-H- (1) -benzopyranon-1 and 2.22 g (0.029 mol) of thiourea in 100 ml of ethanol is boiled 3 hours at reflux, then poured into 200 ml of ice water. The precipitate formed is filtered off, washed with water and recrystallized from a mixture of water and DMF. 2.8 g of product are obtained (yield 59%). IR spectrum, cm (: V ЦИ 3300-3350; 1630.г NMR spectrum (CDC1 $) o, ppm with respect to TMS: 3.3 (replaceable, 2H), Calculated,%: C, 67.48; H 3.78; N 8.74; About 9.99; S 10.01, Found,%: C 67.57; H 3.65; N 8.84; S 10, Obo By the same procedure, the following compounds were prepared. 8- (2-Methylthiaool-1 -yl) -2-phenyl- (1) -benzopyranon-1. mol.m. 319.37 (compound 59). M.p. 1W-153 S. IR spectrum: SvO (acid) 1639.l NMR spectrum (CDCU) b, ppm no with respect to TMS: 2.8 (s, S; 6.8 (1H); 7.2-8.5 (m, 9H). Calculated: C 71.45; H 4.10; N 4.39; O 10-V02; S 10.04. Found: C 71.39; H 4.03; N 4.36; S 10.30. 8-Gimidazo (2,1-b) thiazol-6-yl. -2-phenyl-H- (1) -benzopyranon-. G € oHi2NzOiS, we pray. ZM, 39 (connection 60) „ M.p. 229,233 ° C. IR spectrum, CMW 1630, NMR spectrum (DMSO +) d, ppm with respect to TMS: 7 (s, 1H); 7, -8.8 (m, 11H), Calculated: C 69.75 .; H3.51; N 8.14; 0 9.28; S 9.31. Found,%: C 69.50; H 3.59; N 8.01; S 9.37. 15 2S 24 days NMR spectrum (CDCl1), ppm relative to TMS: 6.8 (s, 1H); , (m, 13H). Calculated,%: C 78.09; H 4.17; N 8.28; About 9.46, Found: C, 78.16; H 4.12; N 8.26. Yu (Indolizin-2-yl) -2-phenyl-H- (1) -benzopyranonone C „H, 5-Shg, mol.m. 337.36 (compound 62). Mp: 20-207 ° C, IR spectrum: 1639. NMR spectrum (CDCl1) 8, ppm relative to TMS: 6.8 (s, 1H); 7.3-8.3 (m, 1H). Calculated: C 81,88; H 4.48; 20 N 4.15; About 9.49. Found: C 82.03; H 4.60; N 4.16. 2-Phenyl-8- (2-phenylthiazol-yl) -. H- (1) -benzopyranone-. S „lN15Og8P, mol.m. 381.6 (63). M.p. 199-202 ° C. IR Spectrum, VC-.Q 1650. NMR spectrum (CFjCOOD) Y, ppm relative to TMS: 7, -8.8 (15H). Calculated D: C 75.57; H 3.96; N 3.67; O 8.39; S 8.41. Found 3: C, 75.42; H 4.03; N 3.64; S 8.15. 8-Ј2,3-Dihydroimidazo (2,1-b) thia-35-sol-6-yl -2-phenyl-H- (1) -benzopyrnonone-, GeoHf4Nt ° z.s mol.m. , CO (compound 6L). M.p. 22b-230 ° C. 40 IR spectrum, 1635. NMR spectrum (DMCO), ppm with respect to TMS: (m, UH); 7 (s, 1H); 7, A-8.3 (m, 9H). Calculated,;: C, 69.34; H 4.07; 45 N 8.09; O 9.24; S 9,26, Found: C, 69.21; H 4.19; N 9.32; S 9.02o PRI me R 10. 10-Acetoxymethyl-2-phenyl-AH-naphtho (1,2-b) pyranone-1. t $ ° 4., mol.m. 33.37 (compound 65). thirty A mixture of 19.8 g (0, OS1 mol) 10-bromomethyl-2-femyl-H-naphtho (1,2-b) pyrano8-G; Imidazo (1; 2-a) pyrilin-2-yl -2 - 55 per-4, 5.3 g (0.051 mol) of acetate-acetaphenyl-H- (1) -benzopyranon-1, li and 110 ml of DM are heated to 5 ° C C22H, 4H4 ° t mol.m. 338.35 (Comm. With stirring. The mixture is allowed to cool neniya 61). D ° room temperature at m. 203-205 C. Sewing for 1 hour. It is poured. IR spectrum - from about 635. five S 24 days NMR spectrum (CDCl1), ppm relative to TMS: 6.8 (s, 1H); (m, 13H). Calculated,%: C 78.09; H 4.17; N 8.28; About 9.46, Found: C, 78.16; H 4.12; N 8.26. (Indolizin-2-yl) -2-phenyl-H- (1) -benzopyranonone C „H, 5-Shg, mol.m. 337.36 (compound 62). Mp: 20-207 ° C, IR spectrum: 1639. NMR spectrum (CDCl1) 8, ppm relative to TMS: 6.8 (s, 1H); 7.3-8.3 (m, 1H). Calculated: C 81,88; H 4.48; 0 N 4.15; About 9.49. Found: C 82.03; H 4.60; N 4.16. 2-Phenyl-8- (2-phenylthiazol-yl) -. H- (1) -benzopyranone-. S „lN15Og8P, mol.m. 381.6 (63). M.p. 199-202 ° C. IR Spectrum, VC-.Q 1650. NMR spectrum (CFjCOOD) Y, ppm relative to TMS: 7, -8.8 (15H). Calculated D: C 75.57; H 3.96; N 3.67; O 8.39; S 8.41. Found 3: C, 75.42; H 4.03; N 3.64; S 8.15. 8-Ј2,3-Dihydroimidazo (2,1-b) thia-5 sol-6-yl -2-phenyl-H- (1) -benzopyr-non-, GeoHf4Nt ° z.s mol.m. , CO (compound 6L). M.p. 22b-230 ° C. 0 IR spectrum, 1635. NMR spectrum (DMCO), ppm with respect to TMS: (m, UH); 7 (s, 1H); 7, A-8.3 (m, 9H). Calculated,;: C, 69.34; H 4.07; 5 N 8.09; O 9.24; S 9,26, Found: C, 69.21; H 4.19; N 9.32; S 9.02o PRI me R 10. 10-Acetoxymethyl-2-phenyl-AH-naphtho (1,2-b) pyranone-1. t $ ° 4., mol.m. 33.37 (compound 65). 0 D ° at room temperature Sewing for 1 hour. It is poured. 21 in a mixture of water and ice, the resulting solid product is filtered off and used in the next stage without further purification. 18.5 g of product are obtained, m.p. 17L (° C. IR spectrum, with „0 (ester) 1740; Sme (pyrone) 1635. NMR spectrum (CDCl-j) §, ppm with respect to TMS: 2.1 (s, 3N); 5.9 (s, 2H); 6.9 (s, 1H); 7.2-8.6 (m, YUN). 10-Oxymethyl-2-phenyl-4H-naphtho (1,2-b) pyranone-4. CGS, H ,, 4P3, mol.m., 302.33 (compound 66), A mixture of 18.9 g (0.054 mol) U-acetoxymethyl-2-phenyl-4H- (1) naphtho (1, 2-b) pyranone-4, 100 ml of ethanol and 39 g (0.07 mol) of potassium the tablets are boiled under reflux for 2 hours. The reaction mixture is then poured into ice water and acidified with 6N hydrochloric acid. The precipitate obtained is filtered, dried and used in the next step without further purification. 16.2 g of product are obtained (yield 99%). . IR spectrum, CM: VOH 3400; Since 1630. NMR spectrum (DMCO) Q, rrga with respect to TMS: 3.5 (s, broad, 1H); 5, (s, 2H),: 7 (s, 1H); 7.2-8, (UN). 4-Oxo-2-phenyl-4H-naphtho (1,2-b) pyranone-4. mol.m. 316.31 (compound 67). A mixture of 16.2 g (0.0536 mol) of 10-hydroxymethyl-2-phenyl-4I-naphtho (1,2-b) pyranone-4, 430 ml of pyridine and 100 ml of water is heated to 60 ° C. 31.7 g (0.2 mol) of potassium permanganate was added in portions over 2 hours, then the mixture was heated under reflux for 4 hours. The mixture is then cooled, treated with an aqueous solution of sodium meta-sulfite until the solution is discolored. The mixture is poured into 1 liter of water, the insoluble products are filtered off and the organic phase is drained. After evaporation in vacuo, the residue is treated with water, acidified with 6N hydrochloric acid. The resulting precipitate is filtered and recrystallized from acetic acid. The weight of the obtained product is 1.1 g (yield 6.5%), so pl. 278-280 ° C IR spectrum, cm: (acid) 1700; (pyrone) 1620. 739846 -2 NMR spectrum (SSR), ppm with respect to TMS: 7J5 (s, 1H); 7.4- 8.4 (m, YUN); 13.5 (interchangeable, 1H). 5Calculated,%: C 75.96; H 3.82; About 20.24, Found: C 75.58; H 3.77, PREMIR 11 about 1- (Ethoxycarbonyl) -ethyl-4-oxo-1-phenyl-4H- (1) -ben zopyran-8-acetate „ C HyyjO, mol.m., 380.38 (compound 68). To the suspension of 30.6 g (0.109 mol). 4-oxo-2-phenyl-4H- (1) -benzopyran-815 Acetic acid in 1.9 l of boiling ethanol is added dropwise a solution of 7.2 g (0.109 mol) of potassium in 100 ml of ethanol. The resulting solution is stirred 30 min, allow it to cool until 20 at room temperature and evaporated in vacuo. The residue is treated with 30 ml of ethanol and evaporated in vacuo, then treated with 30 ml of benzene and evaporated in vacuo. To a residue of 25 ml of methyl isobutyl ketone (MIBK), then a solution of 21.7 g (0.12 mol) of ethyl O-bromopropionate in 55 ml of MIBK. This mixture is heated under reflux for 3 hours, then added 12 g (0.066 mol) of ethyl o-bromopropionate before continuing heating for 5 hours at reflux. Hot filtration is carried out and the filtrate is evaporated under vacuum. The residue is triturated. 35 in hexane to obtain a precipitate, which is filtered, washed with hexane and recrystallized from isopropanol. 36.2 g of product are obtained (yield 87%), m.p. Yu-Yu6 ° C. 40 IR spectrum, V (pyrone) 1730; (pyrone). NMR spectrum (CDCl5) a, pptn with respect to TMS: 1.2 (t, 3N); 1.46 (d, 3N); 4.1 (s, 2H); 4.18 (q, 2H); 5.18 (k, 45 | H); 6.8 (s, 1H); 7.2-8.4 (m, replaced by 8H) „ 4-Oxy-5-methyl-3- 4-oxo-2-phenyl-4H- (1) -benzopyran-8-yl} -5H-furanon-2. they say, m 334.31 (compound 50) o To a suspension of 2.62 g (0.109 mol) of sodium hydride in 226 ml HMPT, a solution of 41.7 g 55 (0.109 mol) of 1- (ethoxycarbonyl) ethyl 4-oxo-2-phenyl-4H- ( 1) benzopyran-8-acetate in 260 ml HMTP0 This mixture is stirred overnight in argon atmosphere at room temperature, and thirty 23 then gently hydrolyzed using 6 L 6N. Suitcase The resulting precipitate is filtered and recrystallized. 28.3 g of product are obtained (yield Y, m.p. 2b5-2b8 ° C. IR spectrum, cm0:} oi 3400-2200; CT: O (lactone) (pyrone) 1600. NMR spectrum (DMCO) 0, ppm with respect to TMS: 1.6 (d, 3N); 5.2 (q, 1H); 7.1 (s, 1H); 7.2-8.6 (9H). Calculated D: C 71.85; H 4.22; About 23.93, Found, $: C 71.55; H 4.1I. Using the same procedure, the following compounds were obtained. 5- (4-Chlorophenyl) -4-hydroxy-3-4-oxo-2-phenyl-4H- (1) -benzopyran-8-yl} -5H-furan-2. C25 4s-Cl ° 5 mol.m. 430.83 (compound / 0). M.p. 2b5-273 ° C. . IR spectrum, U (lactone) 1750; (pyrone) 1660. NMR spectrum (DMCO) o, ppm with respect to TMS: 6.16 (s, 1H); 7 (s, 1H); 7.1-8, (13H). Calculated D: C 69.69; H 3.51; C1 8.23; About 18.57. Found,%: C 69.41; H 3.52; C1 8.27 3-Methyl-4-hydroxy-5-and oxo 2-phenyl-4H- (1) -benzopyran-8-yl7-5H-furanon-2 CtoHwO, mol.m. 334.31 (compound 71). M.p. 160 p .. IR Spectrum, (LECTON) 1760; ) (pyrone) 1640. NMR spectrum (DMCO) a, ppm with respect to TMS: 1.8 (s, 3N); 6.55 (s, 1H); 7.75 (s, 1H); 7.5-8.3 (m, 8H) Calculated D: C 71.85; H 4.22; About 23.93. Found,%: C 71.80; H 4.22. EXAMPLE 12 4- (N, K-diethylamino) -ethoxy-5-methyl-3-4-oxo-2-phenyl-AN- (1) benzopyran-8-yl 5H-furanone hydrochloride 2 C26HZ6C1N (V mol.m. 469.95 (compound / 2). A mixture of 20 g (0.06 mol) of 4-hydroxy-5-methyl-3-4-oxo-2-phenyl-4H- (1) -benzopyran-8-shTG} -5H-furanone-2, 9, 93 t (0.72 mol) of potassium carbonate and 0.36 g (0.002 mol) of potassium iodide in 490 ml of MIBK are refluxed for 1 h. Then a solution of 10.6 g (0.078 mol) of 2-diethylamino is added. 739Я46 ethyl chloride in 90 ml of MIBK and continue heating for 7 hours. The minerals are filtered off by hot filtration and the filtrate is evaporated in vacuo. The residue is washed twice with hexane, then solubilized in a minimum amount of acetone and diluted with hexane. 10 light insoluble materials are filtered off, the filtrate is evaporated in vacuo and the residue is dissolved in 200 ml of ethanol. This product is cooled in an ice bath and HCl is bubbled through to pH 2. A precipitate is obtained when ether is added, the precipitate is filtered and the mixture is crystallized from ethanol-ether. 16.9 g of product are obtained (yield 60%), m.p. 168-169 C. 20 IR spectrum, cm: V (lactone) 1740; s.o (pyrone) 1640. NMR spectrum (DMCO-CDC1,) Y, ppm relative to TMS: 0.9 (t, 6H); L 5 (d, 3N); 2.6-3.3 (m, 6H); 4.2 25 (t, 2H); 5.2 (q, 1H); 6.75 (s, 1H); 7.3-8.2 (8H) „ Calculated D: C, 66.45; H 6.00; - C1 7.55; N 2.98; About 16.02. Found: C, 66.30; H 6.20; C1 7.55; N 2.83, Using this technique, the following compounds are obtained. Ј2.5 Dihydro-5-methyl-2-oxo-3-4-oxo-2 phenyl-4H- (1) benzopyran-8-yl | furan-4-ylTethyloxyacetate. 35 ScNo®7 mol.m. 420.4 (compound 73). M.p. 257-259 S. IR spectrum: Woy 2400; V (lactone) 1740; v (acid) 1710, ° (pyrone) 1620, NMR spectrum (DMCO) and ppm with respect to TMS: 1.6 (d, 3N); 4 (interchangeable, 1H); 4.66. (S, 2H,); 5.4 (q, 1H); 7.08 (s, 1H); 7.2-8.4 (m, 8H). 45 m.p. 153 ° C. , IR spectrum, cm: (ester and lactone) 1755; r-l (pyrone) 1640. NMR spectrum (CDCl 3), ppm relative to TMS: 1 (t, 3N); 1.7 (d, 3N); 3.9 (q, 2H); 4.5 (s, 2H); 5.18 (q, 1H); 6.9 (s, 1H); 7.2-8.5 (8H). {2,5-Ligidro-5-methyl-2-oxo-3-U | -oxo-2-phenyl-4H- (1) -benzopyran-8- / 55 orZhfuran-4-pc} oxyacetic acid. CwHf607, mol.m. 392.39 (Compound 74). Calculated D: C, 67.34; H 4.11; About 28.55. thirty 25 Found: C, 67.20; H 4.00, 0-Ј2,5-Dihydro-5-methyl-2-oxo-3- 4-oxo-2-phenyl-4H- (1) -benzopyran-8-yl furan-4-yl | dimethylcarbamothioate. Cr% H AM058, mol.m. 421.46 (compound 75), M.p. 173-175 ° C. IR spectrum, v с «-0 (lactone) 1740; (pyrone) 1bZO „ NMR spectrum (CDC15) $, ppc in relation to TMS: 1.66 (d, 3N); 2.8 (s, 6H),: 6.16 (q, 1H); 6.8 (s, 1H); 7.2-8.4 (m, 8H). Calculated D: C 65,54; H 4.70; N 3.32; O 18.98; S 7,61 Found: C 65.42; H 4.52; N 3.32; S 7.64. Example 13. 8-Acetylthiomethyl-4-oxo-2-phenyl-4H- (1) -benzopyran „ C 8H140% 5, mol.m. 310.38 (compound 76). 48 g (0.152 mol) of 8-bromomethyl-2-phenyl-4n- (1) -benzopyranone-4 portions are added to a mixture of 17.4 g (0.152 mol) of potassium thioacetate in 120 ml of DM "b". stirring. The mixture is stirred for 1 hour at room temperature and then poured into a water-ice mixture. The precipitate obtained is filtered and recrystallized from ethyl acetate. Obtain 38 g (yield 80S), since 160 ° C „ IR spectrum, (ETHER) 1690; 3Св0 (pyron) 1655. NMR spectrum (CDC1) Ј, ppm relative to TMS: 2.4 (s, 3N); 4.5 (s, 2H): 6.9 (s, 1H); 7.2 - 8.4 (m, 8H) EXAMPLE 14, 8-Mercaptomethyl-2 Phenyl-4H- (1) -benzopyranone-4. c "6Hi2 ° zs mol.m0 268.34 (compound 77). To a mixture of 38 g (0.122 mol) of 8-thio-acetylmethyl-2-phenyl-4H- (1) -benzopyranon-4 and 230 ml of ethanol are immediately added 150 ml of ethanol, saturated with anhydrous HC1. The mixture is heated for 18 hours under reflux. This mixture is cooled and the resulting precipitate is heated and recrystallized from ethanol. Receive 39.7 g (yield 97%), so pl. 162 ° C. IR spectrum, 3 s 01640. NMR spectrum (CDC1S) $, ppm relative to TMS: 2 (t, 1H); 4.1 (d, 2H); 6.8 (s, 1H); 7.2-8.4 (m, variable, 8H). Calculated D: C 71.62; H 4.51; O 11.92; S 11.95. 739846.26 Found D: C 71.45; H 4.48; S 11.84. Using the same metaldica, the following compounds are obtained. Ј4 Oxo-2-phenyl-4H- (1) -benzopyran-8-yl methylmethylthioacetate. mol.m. 340.4 (Compound 78). 0T.pl. 110 ° С „ 1K-spectrum, cm: (ETHER) 1720,) (pyrone) 1650. NMR spectrum (CDC1.) 8, ppm relative to TMS: 3.2 (s, 2H} {3.7 (s, 5 ZN); 4.2 (s, 2H); 6.8 (d, 1H); 7.2-8.4 (m, 8H). 4-Oxo-2-phenyl-4H- (1) -benzopyran-8-yl methylthioacetic acid. C 8H1404.S, mol.m. 326.37 (comp. 79). M.p. 202-2044. IR spectrum, ZUO-2400; (acid) 1720; l) (pyrone) 1640. 5NMR spectrum (SSR) o, ppm relative to TMS: 3.2 (s, 2H); 4.25 (s, 2H); 6.8 (s, 1H); 7.2-8.4 (m, 9H). Calculated D: C 66.24; H 4.32; . O 19.61; S 9,81. 0 Found: C 66.51; H 4.34; S 10.11. Oxalate 8- (2-diethylaminoethoxymethyl) -2-phenyl-4H- (1) -benzopyranone-4. C2 jH2yN07, mol.m. 441.48 (connection 80). Mp 162-164 ° C. IR spectrum: V 1660. NMR spectrum (DMSO) u, ppm relative to TMS: 1.2 (t, ЗН); 2.95-3.5 0 (. 6H); 3.8-4.2 (m, 1H); 5.05 (s, 2H); 5.4 (variable, 2H); 7.1 (s, 1H); 7.5-8.5 (m, 8H). Calculated D: C 65.29; H 6.16; N 3.17; About 25.37. 5 Found: C 65.18; H 6.10; N 3.07 8-2-hydroxy-1- (hydroxymethyl) ch-ethoxymethyl -2-phenyl-4H- (1) -benzopyranone-4. mol.m. 326.33 (compound- 0 81). T0pl. 1b2 ° C. IR spectrum, see: it is 3300; ) with ", about 1620, NMR spectrum (DMSO) 0, ppm relative to TMS: 3.3-3.7 (m, 5H); 4.5 (variable, 2H); 5 (s, 2H); 6.93 (s, 1H); 7.2-8.2 (m, 8Mb Calculated D: C 69.93; H 5.56; About 24.51., 27 Found: C, 70.00; H 5.57. EXAMPLE 15 4-Oxo-2-phenyl-4H- (1) benzopyran-8-acetamide. C "n 13N03, mol. 279.28 (compound R2). A suspension of 5 g (0,0178 mol) of 4-cc-2-phenyl-4I- (1) -benzopyran-8-acetic acid in 180 ml of dioxane is heated until it dissolves. A solution of 3.5 g (0.0124 mol) N, N -carboxyl diamidazole in 30 ml of dioxane is added and the mixture is heated for 1 hour to 80 ° C, then cooled to 20 ° C and about 10 ml are slowly added at -33 ° C ( 4 mol) of liquefied anhydrous ammonium; The mixture is stirred for 10 minutes at 20 ° C, then for 3 hours at 80 ° C. The mixture was incubated overnight, filtered, washed with hexane, then with a hot 5% sodium bicarbonate solution and then with water, then the substance was recrystallized from ethanol. “3.3 g are obtained (yield 66), mp. 232-258 ° C. IR spectrum: Q and 3370 to 320 (acid) 1660; Q.Q- (pyrone) 1630. NMR spectrum (CDC13 + CF3COOD) ff, ppm relative to TMS: 4.33 (s, 2H); 7.5-8.7 (m, 9H); 11.5 (2H). Calculated: C 73,13; H 4.69; N 5.01; About 17.19. Found, C 73.13; H 4.69; N 5.00 EXAMPLE 160 4-Oxo-2-phenyl-4H- (1) -benzopyran-8-thioacetamide. mol.m., 295.35 (compound 83). After a mixture of 60 g (0.229 mol) of 4-oxo-2-phenyl-4H- (1) -benzopyran-8-acetonitrile, 16.2 ml (0.116 mol) of triethylamine and 900 ml of pyridine, the HjS is bubbled through. A stream of nitrogen is then passed through this mixture and the mixture is poured into 5 liters of ice-cold water, acidified to pH 5-6 with hydrochloric acid, filtered, washed with ether, dried and crystallized from 6N. DM, Obtain 24.7 g (yield 36), so pl. 223-224E IR spectrum, Vi } from 01b20. NMR spectrum (DMCO) 0, ppm relative to TMS: 4.15 (s, 2H); 6.9 (s, 1H); 7.2-8.4 (m, 8H); 9.4 (s, 2H). Calculated: C 69.13; H 4.44; N 4.74; 0 10.83; S 10.86. GI 3250 and 3080 28 Found: C, 69.22; H 4.38; N 4.80; S 10.68. EXAMPLE 17 2-phenyl-4- (phenyl-2-thia-sol-yl) methyl -8-4H- (1) -benzopyrananone-4. C2yH, 7NOt, mole “, m 395.46 (compound 84). A mixture of 5 g (0,0169 mol) of 4-oxo-2phenyl-4H- (1) -benzopyran-8-thioacetamide, 4 g (0,0203 mol) of d-bromoacetophenone and 120 ml of methoxyethanol is | for 5 hours under reflux, then cooled and left overnight at -20 ° C. The solid obtained substance is filtered and then recrystallized from MIBK, then from acetone. 3.3 g are obtained (yield 49). (. IR spectrum, cm: Vc ol620, NMR spectrum (CDCl1) &, ppm relative to TMS: 4.7 (s, 2H); 6.75 (s, 1H); 7.1-8.3 (m, 14H). Calculated: C 75.92; H 4.33; 5 N 3.54, O 8.09; S 8.11, Found C, 75.73; H 4.23; N 3.52; S 8.31 Using the same procedure, the following compounds were obtained. ЈC4-Oxo-2-Phenyl-4H- (1) -benzopiran-8-yl methylj-2-thiazole-4-ethylcarb-oxylate C22H, 7NO,}, S, mol. 391.43 (Compound 85). M.p. 152-153 С „ 5 IR spectrum, (ether) 17U; (pyrone) 1b40 „ NMR spectrum (CDCl1) 8, ppm relative to TMS: 1.3 (t, 3N); 4.4 (q, 2H); 4.73 (s, 2H); 6.7 (s, 1H); 0 7.1-8.3 (m, 9H). | 4-Oxo-2-phenyl-4H- (12) -benzopyran-8-yl | methyl -2-thiazole-4-carboxylic acid. G2.oHfs-NO S, MOLSM, 362, -38 (Comp. 86). M.p. 237-240 ° C. IR spectrum: VQW 3100 to 2400; v (acid) 1720; (pyrone) 1620s 0 NMR spectrum (DMCO) Q, ppm relative to TMS: 4.7 (s, 1H); 6.9 (s, 1H); 7.2-8.15 (m, 8H); 8.2 (s, 1H). Calculated: C 66,10; H 3.61; N 3.85; O 17.61; S 8,82. Found: C 69.83; H 3.60; | N 3.87; S 8.60, Example 18. C. 4-Oxo-2-phenyl-4H- (1) -benzopyran-8-yl} methylene -2-hydrazinecarbothioamide. mol.m. 323.36 (compound 87). A suspension of 5 g (0.02 mol) of C4-oxo-2-phenyl-4H- (1) -benzopyran-8-ylJ carboxaldehyde in 120 ml of dioxane is heated to dissolve. The solution is cooled to 25 ° C, a solution of 2 g (0.022 mol) of thiosemicarbazide in 40 ml of dioxane is added, heated for 5 minutes at 90 ° C, then returned to 25 ° C with stirring. The precipitate is filtered off and recrystallized from methoxyethanol. 48 g are obtained (yield 41%), mp 258-2b2 ° C. IR spectrum, J CN 3400 to 3100; 7640. Calculated D: C 63.14; H 4.05; N 13.00, O 9.90; S 9.92 „ Found,%: C 63.12; H 4.04; N 13.00; S 9.87, Using the same procedure, the following compounds were obtained. 4,5 Dihydroimidazol-2-yl-hydrazone-4-oxo-2-phenyl-4H- (1) -benzopyran-8-yl-carboxaldehyde bromohydrate .- mol.m. 413.28 (compound 88). M.p. 301-303 ° C. IR spectrum, NH 3300; VC N-c o1660 and 1640. NMR spectrum (DMSO) o, ppm relative to TMS: 3.4 (s, 2H); 3.8 (s, 4H); 7.1 (s. 1H); 7.3-9 (m, 1H of which is variable, 10H) „ Calculated D: C 55,21; H 4.15; Br 19.34; N 13.56; About 7.74, Found,%: C 54.96; H 4.09; N 13.62, Example 19. (4-Oxo-2,3,5,6-tetrahydro-4H-pyran-2-yl) -8-phenyl-2 4H- (1) -benzopyranon-4. m ° l.m. 320.33 (compound 89). 20 g (0.08 mol) of 4-oxo-2-phenyl-4H- (1) -benzopyran-8-carboxaldehyde was added in portions to a mixture of 22.8 (0.16 mol) of anhydrous trimethylsilyloxy-2 -butadiene-1,3 and 12 g, (0.088 mol) of anhydrous ZnCl 2. in 500 ml of anhydrous dioxane. The mixture was heated under reflux for 8 hours under a nitrogen atmosphere and then left under stirring for 48 hours at room temperature. The slightly insoluble product is filtered off and 1 l of a solution of 5% NaHCOj is added to the filtrate. The resulting insoluble product is filtered off and the filtrate is extracted using ethyl acetate, then dried and evaporated under vacuum. The residue is dissolved in 300 ml of methanol and refluxed for 3 hours. After cooling to 25 ° C, 3.6 ml of acetic acid is added and left overnight with stirring. The mixture is evaporated under vacuum and the residue is recrystallized from MIBK. 9.2 g are obtained (yield 30%), mp, 220-2214. ( IR spectrum, cm: v (pyranone) 7695; (pyrone) 1640. 5 NMR spectrum (CDC1 $) $, pptn relative to TMS: 2.3-3, - (m, 4H); 3.7-5.7 (m, 2H); 5.3 (dd, 1H); 6.8 (s, 1H); 7.1-8.3 (m, 8H). Calculated D: C 74,98; H 5.03; 0 About 19.98, Found: C 75.03; H 4.81, Example 20. (4-Oxy 113,4,596-tetrahydro-2H-pyran-2-yl) -8-phenyl-2-4H- (1) -benzopyranone-4. 5 CggHigO, mol.m. .322.34 (compound 90). A mixture of 6.8 g (0.021 mol) of compound-; Neni 87, 116 md dioxane and 58 ml methanol is heated to dissolve. The mixture is cooled to 35 ° C and added in portions of 0.9 g (0.023 mol) NaB1C °. The mixture is then heated under reflux for 3 hours. After cooling, water is added and the resulting precipitate is filtered off and recrystallized from isopropanol. Get 3 g (yield 43%), so pl. 187-190 ° C. IR spectrum, 3400-3200; 1610. NMR spectrum (CBC1) $ ppm from TMS: 1-2.76 (m, 4H), 3.2-4.4 (m, 1H of which is variable 4H) $ 4.9 (d.d. 1H); 6.8 (s, 1H); 7.2-8.2 (m, 8H). Calculated D: C 75.52; .H 5.63; 0 19.85 Found: C, 74.82; H 5.52. EXAMPLE 21 Oxo-4-pkso-2-phenyl-4H- (1) -benzopyran-8-yl | -4-buten-2-ovic acid. C, .05, molol. 320.29 (compound 91) o A mixture of 2 g (0.0076 mol) of 8-acetyl-2-phenyl-4H- (1) -benzopyranone-4, 1.4 g (0.019 mol) of glyoxylic acid and 25 ml of acetic acid is subjected to boiling under reflux. for 2 hours. Then the mixture is poured into water and the precipitate formed is filtered off. The precipitate is dissolved at nag31 Cook with a solution of 5% NaHCO and acidify using acetic acid. The precipitate is filtered off, washed with water and recrystallized from a mixture of dioxane - hexane. Half 0.5 g (yield 20.6%), so pl. 217-21P.C IR spectrum, cm: v (acid) 17U; s.o (ketone) 1760; ) (pi-- ron) 1620. NMR spectrum (DMCO) a, rrtp relative to TMS: 3.8 (variable, 1H); 6.5-8.5 (m, 11H). Calculated,%: C 71.24; H 3.78; About 24.98. Found: C 71.17; H 3.52. Example 22 2-p4-oxo-2-phenyl F- (1) benzopyran-8-yl3 2-hydroxy-vinegar acid. S17N12P5 mol.m. 296.2P. (compound 92). A mixture of 8.75 g (0.13 mol) of potassium cyanide, 125 ml of water, 1.25 ml of dioxane, 53 g (0.5 mol) of Na2C03 and 15.32 g (0.061 mol) of oxo-2-phenyl - H-benzopyran-8-carboxaldehyde is stirred at room temperature for 1 hour. Then 75 ml of acetic acid are added and this mixture is stirred for 6 hours at room temperature. The mixture is poured into kl of water. The precipitate obtained is washed with water and recrystallized from acetic acid-water. Get 2.5g (yield 1k%). IR spectrum, cm-: Choi (KMc; iOTa) 1720} l) (pyrone) 1620. NMR spectrum (DMCO) $, rrga relative to TMS: 3, (variable, 1H); 5.6 (s, 1H); 7 (s, 1H); 7.3-8.3 (m, 1H of which is variable, 9H). Calculated D: C 68.92; H 4.08; About 27.00. U ID: C 68.98; H 4.19. EXAMPLE 23 2- -Oxo-2-phenyl-1H- (1) -benzopyran-8-yl -2-hydroxy-ethyl acetate. , 605, my 32.32. (compound 93). A mixture of 29 g (0.098 mol) of 2-A-oxo-2-phenyl-M- (1) -benzopyran-8-yl-2-hydroxyacetic acid and 35 ml of concentrated 5 to 5 ml of ethanol is boiled for 5 hours with reflux condenser. The mixture is then poured into water, extracted using ethyl acetate, dried, evaporated and the resulting white solid is recrystallized from mixture . - - , C MIBK - hexane. Receive 20.3 g (yield), so pl. 135 ° C. IR spectrum, cm):) (ether) 1730, (pyrone). EXAMPLE 2U H- (1) -benzopyran ethyl acetate. mol.m. 322.3 (compound 9M. j i I. 2-Oks 1-8-igG | -2-s 0 | -Oxo-2-phenyl-oxo10 0.79 g (0.0077 mol) CrO, 0.8 g (0.0077 mol) of chlorotrimethylsilane is dissolved in 10 ml of methylene chloride. A solution of 2.5 g (0.0077 mol) of J5 oxo-phenyl-2-4H- (1) -benzopyran-8-yl3-2-hydroxy-2-ethyl acetate in 20 ml of methylene chloride is added with cooling - Research until a red solution is obtained. The solution is stirred at room temperature for 3 hours and 50 minutes. The mixture is passed through a silica gel column and eluted with CHC1. The solution is evaporated and the residue is recrystallized from hexane. 0.9 g is obtained (yield 36.3%). m.p. 85-90 ° C. IR spectrum, cm: (ether) 1730; ketone) 1690; (pyrone) 1640. NMR spectrum (CDCLj), rrp relative to TMS: 1.3 (t, W), k, 3 (k, 2H); 6.8 (s, 1H); 7.25-8.7 (m , 8H). Example 25. 2-P Oxo-2-phenyl-F- (1) -benzopyran-8-yl -2-oxo-acetic acid. 35 C LTS00, mol. M. 29.25 (compound 95) " A mixture of 9.3 g (0.0288 mol) of oxo-2-phenyl-H- (1) -benzopyran-8-yl -2-oxo-ethyl acetate, A, 85 g of 40 (0.057 mol) of sodium bicarbonate, 150 ml of ethanol and 115 ml of water is refluxed for kh 30 min. Then the ethanol is evaporated, 150 ml of water is added, the mixture is acidified with 1/2 HC1 and the resulting precipitate is filtered and recrystallized from dioxane. Obtain 2.3 g (yield 27%), so pl. 232-235 ° C. (. IR spectrum, cm: (acid) 50 (ketone) 1690; Sm) (pyrone) 1660, NMR spectrum (DMCO), ppm relative to TMS: 7.3 (s, 1H); 7, -8.5 te (m, 1H of which is variable, 9H). Calculated,%: C 69.39; H 3.91; About 27,19s Found,%: C 69.11; H 3.95. 33 Example 6. 2-Methyl-4-oxo-2 phenyl-4H- (1) -benzopyran-8-yl 7-methylpropanoate. С1ан48 ° And they say ,, m. 322.34 (compound 96). A solution of 6.7 g (0.023 mol) of 4-oxo-2-phenyl-4H- (1) -benzopyran-8-methyl acetate in 120 ml of DM is slowly added to a suspension of 2.33 g (0485 mol sodium hydride in 10 ml DM. This mixture was stirred for 1 hour at room temperature, then 6.6 ml (0.1 mol) of methyl iodide in 5 ml of DMF was added dropwise. This mixture was stirred for 6 hours at room temperature and then 6.6 ml of C 1 H in 5 ml of DMF was added. The mixture is stirred overnight, 15 ml of acetic acid are added, the mixture is concentrated to 50 ml, water is added and the ethyl acetate is extracted. The extract is dried, evaporated in vacuo and recrystallized from methanol. Get 3.5g (yield 42%), so pl. 157 ° C. IR spectrum, c & 0 (ether) 1720; (pyrone) 1650. NMR spectrum (SPS1e) 8, ppm relative to TMS: 1.75 (s, 6H); 3.6 (s, 3N, 6.87 (s, 1H); 7.2-8.1 (m p, H). Example 27. 2-Methyl-2-Ј4-ox-2-phenyl-4H- (1) -benzopyran-8-yl - propionic acid. mol.m. 308.318 (compound 97). A mixture of 5.7 g (0.0177 mol) of 2-methyl 2-4-oxo-2-phenyl-4H- (1) -benzopyran-8-yl | -2-methylpropanoate, 95 ml of acetic acid, 95 ml of concentrated sulfuric the acid and 95 ml of concentrated hydrochloric acid are refluxed for 2 hours. The mixture is then stirred for 12 hours at room temperature and again heated to reflux for 3 hours. The mixture is cooled and the precipitate formed is filtered and stabilized. in 250 ml of 5% bicarbonate solution. Then, 1/2 HC1 is acidified and the precipitate is dried, washed with water and recrystallized with acetic acid. 3.1 g are obtained (yield 56.8%), MRq 255-260 ° C. IR spectrum, cm: V с o (acid) 1720; t-Q (pyrone) 1620. NMR spectrum (CF3COOD), ppm relative to TMS: 2 (s, 6J); 7.68 .6 (m, 9H); 11.7 (variable, 1H), 7398463 Calculated,%: C 74.01; H 5.23; About 20.67. Found: C, 73.93; H 5.25, 5 Example 28. 4-Oxo-2-phenyl H- (1) -benzopyran-8-carboxaldehyde oxime (8) „ C, 6H „N03, mol. 265,256 (compound 98). 10 A mixture of 10 g (0, OA mol) A-oxo-2-phenyl- (H- (1) -beneopyran-8-carboxaldehyde, 3.7 g (0.05 mol) of hydroxylamine hydrochloride, 7.1 g (0.10 mol) of sodium acetate, 20 ml of water and LO ml of 15 ethanol are refluxed for 1 hour. After the resulting product is dried and recrystallized from dioxane, 6.3 g are obtained (yield 59.4%) , MR 20 230-238 ° C.q IR spectrum, cm: Vftu 3200 to 2800. NMR spectrum (CFjCOOD), ppm relative to TMS: 7.8-9.5 (m, YUN). 2 $ Calculated,%: C 72.44; H 4.18; N 5.28; About 18.10. Found,%: C 72.74; H 4.24; N 5.03. Using the same method, 8-acetyl-2-phenyl-1H- (1) -benzopyrano-oxime (8) was prepared. C17H13Sh2 mol.m. 279.282 (compound 99). Calculated,%: C 73.10; H 4.69; N 5.02; About 17.19. 35 Found: C 73.00; H 4.70; N 4.99, PRI me R 29. 3 (Morpholin-4-yl) -2-p-oxo-2-phenyl-1H- (1) -benzo-40 pyran-i-yl glutaronitrile. с2Чн2.Лтг. ° 5 mol.m. 399.3 (compound 100). A solution of 1.33 g (0.025 mol) of acrylonitrile in 10 ml of dioxane is added 45 dropwise to a mixture of 7 g (0.02 mol) of (morpholine-yl) -2-C Oxo-2-phenyl-. 4H- (1) -benzopyran-8-yl-acetonitrile. After 18 hours at room temperature, the poorly dissolved material is filtered and evaporated under vacuum. The residue is recrystallized from isolropanol. Obtain 3.1 g (yield 38.8,%), MRK 11P ° C. 55 IR spectrum,) 2250; Ol 1640. NMR spectrum (CDCl1), ppm relative to TMC g 1.8-3.2 (m, 8H); 3.9 (t, AH); 7 (s, 1H); 7.4-8.6 (m, 8H). one Example 30. A-Oxo- -fVoKco-2-phenyl-4H- (1) -benzopyran-8-yl butyric acid. mol.m. 322.3 (compound 101). A mixture of 3 g (0.0075 mol) of compound 100, 30 ml of 6N hydrochloric acid and 30 ml of acetic acid is refluxed for 4 hours. This mixture is then poured into ice-water, the product is dried, transferred to the solution is 5% NaHCOg and acidified. The precipitate formed is dried and recrystallized from MIVC dioxane mixture. 1.1 g (yield: 45.5%) are obtained, MRF 207-209 ° C. IR spectrum, (acid) 1720; } (ketone) 1680;.} C & 0 (pyrone) 1b20 „ NMR spectrum (DMSO), ppm relative to TMS: 2.4-3.6 (m, 4H); 7.1 (s, 1H); 7.4-P.4 (m, 8H); 12.1 (variable, 1 N). Calculated,%: C, 70.80; H 4.38; About 24.82, Found: C, 70.50; H 4.43, Example 31 Hydroxy-4-pkso-4-phenyl-2-4H- (1) -benzopyran-B-yl} butyryic acid. , they say „m ,, 324,32 (compound 102). By treating 5 g (0.0155 mol) of compound 101 with 9.5 g (0.0468 mol) of aluminum i-oopropylate in 100 ml of isopropanol and 40 ml of dioxane for 6 hours under reflux, is obtained after recrystallization from hexane 1, 9 g of isopropyloxyether (MRK 145 ° C) "The substance is transferred into 10 ml of water, 17 ml with 0.45 g of sodium bicarbonate. The medium is heated under reflux for 4 hours 30 minutes, evaporated and the residue is taken up in water. The insoluble material is filtered off, acidified with acetic acid, dried and recrystallized from dioxane. Obtain 0.7 g MR 198-202 ° C, IR spectrum, cm: it is 3350; with "o (acid) 1700; Nc. & (pyrone) 1620. NMR spectrum (DMCO) a, ppm relative to TMS: 1.7-2.9 (m, 4H); 5.3 - 5.8 (m, 1H of which is the variable 2H); 7.1 (m, - 1H); 7.4-8, b (m, 8H); 11.8 (variable, 1H). Calculated,%: C, 70.36; H 4.97; About 24.67. Found: C 70,56; H 4.72 „ Primer ep 32 „2-Acetamido-2-ethoxycarbonyl-2- (7-oxo-2-phenyl-H- (1) -benzopyran-8-yl ethylpropionate nat mol.m., 51, 6 (compound 103) o 17.5 g (0.08 mol) of diethyl acetamidomalonate are added at 20 ° C in 10 minutes to 20 minutes to a suspension of 3 g (0.08 mol) of sodium hydride in 100 ml of toluene. The mixture is kept under stirring for 1 hour, then 25 g (0.08 mol) of 8-bromomethyl-2-phenyl-AN-15 (1) -benzopyranone is added for 1 h. The mixture is boiled under reflux for 8 h and then filtered in a hot state, the filtrate is evaporated under vacuum, the residue is taken up in water, the solid is dried and recrystallized from ethanol. Get 2, g (yield 67.6%), MRR IR spectrum, cm-: c 3370; vc-o 25 (ether) 1720 and 1760; C 0 (amide) 7670; s-o (pyrone) EXAMPLE 33 2-Amino-3 C Oxo-2-phenyl-H- (1) -benzopyran-8-yl-pyonic acid (hydrochloride). JQ C (8IL, 6C1NO, mole, 78 (compound „ A mixture of 10 g (0.022 mol) of compound 103 and 00 ml of 1/2 HC1 was heated under reflux for hours. After overnight at rest, the resulting precipitate was dried and recrystallized from a mixture of AOH — water. Get k, b g (yield 57.6%), MRQ. IR spectrum, it, N "3500-0 2500, - (acid) b: b0 (pyrone) 1625. NMR spectrum (DMCO) $, ppm relative to TMS: 3,4-M (m, 3N); 7.1 (s, 1H); 7.4-U (m, 4H of which is variable in variables, 1H). Calculated D: C, 62.52; H 4.66; C1 10.26; N 4.05; About 18.51. Found: C 62,66; H 4.89; 50 C1 10.35; N 4.11. The following compounds are prepared as in Example 1. 2- (2-Aminophenol) --4-oxo-4H- (1) - benzopyran-8-acetic acid. C 7H15N04, mol. M, 295.28 (Compound 105). FF, 189 ° С „ -one IR spectrum, cm :) s-o (acid) 17U; with "h (pyrone) 1bGo" 37 Calculated, 3: C, 69.14; H 4.44; N 4.74; O 21, 61, Found: C 68.92; H 4.25; N 4.45. 2- (2-Chlorophenyl) -4-oxo-4H- (1) -be zopyran-B-acetic acid. C104, mol. 31,715 (compound 1 is about). PFq 169 ° C. IR spectrum, cm:) (acid) (pyrone) 1620 ° L NMR spectrum (DMCO) o, ppm relative to TMS: 4.3 (s, 2M); 7.5-8.7 (m, 8H); 11.7 (variable, 1H). Calculated D: C, 64.87; H 3.52; C1 11.27; About 20.34, Found: C 65.09; H 3.48; C1 11.53o 2- (2-Chlorophenyl) -4-oxo-4H- (1) -be zopyran-8-acetic acid. C HffClOj}, mol.m. 314.715 (compound 107). PFG 220-222 ° C. IR spectrum, cm: Vc-o (acid) 1720; (pyrone) 1620. NMR spectrum (DMCO) $, ppm relative to TMS: 4 (s, 2H); 7.5 (s, 1H), 7.3-8.3 (m, 7H); 13 (variable, 1H Calculated D: C, 64.87; H 3.52; C1 11.27; About 20.34, Found 2: C, 64.59; H 3.53; C1 11.28 2- (2-Acetamidophenyl), -5-oxo-4H- (1) -benzopyran-8-acetic acid. I C HfgNOj-, mol.m. 337,318 (comp. 109). PFG 196-201.S. IR spectrum, cm: Y (acid) 1720; (amide) 1660; (pyrone) 1620. NMR spectrum (DMCO) 0, ppm relative to TMS: 2 (s, ZI); 3.8 (s, 2H); 6.5 (s, 1H); 7.3-8.2 (m, 7H); 8.8 (variable, 1H); 11.5 (variable. 1H). Calculated D: C 67.65; H 4.48; C1 4.15; About 23.72. Found: C, 67.42; H 4.24; € 1 4, and. 2- (4-Acetylphenyl) -4-oxo-4H- (1) is benzopyran-B-acetic acid. CA4H "0S mol.m. 322,302 (compound 109). PFg 253-255 ° C. IR spectrum,: Vc-o (PIRON) 1620. NMR spectrum (CF3COOD) (G, ppm relative to TMS: 2.8 (s, 3N); A, 3 (m, 2H); 7.7-8P5 (m, PH). Calculated D: C 70.80; H 4.38; O, 24.82; Found: C, 70.61; H 4.31. 2- (3-Acetamidophenyl) - -oxo-4H-5 (1) -benzpyran-8-acetic acid. , 5-MO-, mol. M. 337.318 (compound 110). PFQ 284-288 ° C. m IR spectrum, (acid) 10 1720; (amide-pyrone) 16.30, NMR spectrum (DMCO) Ј, ppm relative to TMS: 2 (s, 3N); if (s, 2H); 6.8 (s, 1H); 7.1-8.1 (m, 7H); 9.8 (variable, 1H); 12 (variable, 1H). 15 Calculated D: C, 67.65; H 4.48; N 4.15; About 23.72. Found: C, 67.70; H 4.40; N 4.12. - 2- (2-Diethylaminoethoxyphenyl) -C-oxo-Ж-О) -benzopyran-8-acetic acid (hydrochloride), C23H25-ClNOy. Mol. 431,903 (compound 111). 25 PFq 178-182 ° С „ IR spectrum, with (acid) 1720; (pyrone) 1640. NMR spectrum (DMCO), ppm relative to TMS: 1 (t, 6H); 2.8-3.8 (m, 6H); 3.9-4.2 (m, 1H); 6.9-8 (m, 8H); 30 and (variable, 1H). Calculated D: 63.96; H 6.07; C1 8.21; N 3.24; About 18.52. Found: C 63.96; H 6.12; C1 8.19; N 3.24. 35 2- (3-Nitro-4-chlorophenyl) -4-oxo-4H- (1) -benzopyran-8-acetic acid. C 7H10C1N04, 359.715 (compound 112). PFQ 232-234 ° C3 40 IR spectrum, (acid) 1720; Vc, 0 nMP ° H) 1640. NMR spectrum (PMSO), ppm relative to TMS: 4 (s, 2H); 7-8, and (m, 7H); 12.1 (variable, 1H). 45 Calculated D: C, 56.76; H 2.80; C1 9.86; N 3.89; 0 26, 69. Found: C, 56.82; H 2.69; C1 9.78; N 3.90. 2- (2,4-Dimethoxyphenyl) -4-oxo 4H-50 (1) -benzopyran-8-acetic acid. C) H (6 ° 6 mol.m. 340.185 (compound 113) o PFG 225-227 ° C. IR spectrum, V (acid) 55 1710; ) with „0 (pyrone) 1620. NMR spectrum (DMCO) Q, ppm relative to TMS: 3.5 (s, 2H) | 3.9 (s, ZN), 4 (s, ZN); 6.8 to 8 (7H); 12.2 (variable, 1H). 39 Calculated D: C 67.05; H A, 74; About 28.2b Found: C, 67.23; H 4.63. 2- (C-Dimethylaminoethoxyphenyl) oxo-H- (1) -benzopyran-8-acetic acid (hydrochloride) „ SazN26S1MOG, mol. Mo 31.92 (compound PFq 194-199 ° Co ( IR spectrum, cm: V (acid) 1720; (pyrone) 1630. NMR spectrum (DMCO) 8, ppm relative to TMS: 3-, 7 (m, 8H); 6.8- 8.3 (m, 8H); 10.4-10.8 (variable, 1H). Calculated,%: C 63.89; H 6.07; C1 8.21; N 3.24; About 18.57. Found: C 63,50; H 6.04; C1 8.30, N 3.45. 2- (4-Carbamoylphenyl) -4-oxo-4H- (1) -benzopyran-8-acetic acid. C, VN, TSh, mol.m. 323,292 (conjunction 115). PF (j 228-290 ° С „ IR spectrum, cm: (acid) 17U; (amide + pyrone) / Calculated,%: C, 66.87; H 4.05; N 4.33; 0 24.75. Found: C 66.35; H 4.35; N 4.46 „ (2-Methyl-thiazolyl-1} -1-phenyl--oxo-H- (1) -benzopyran-8-acetic acid. C2IH15N04S mole "m" 377.398 (compound 116). PFQ 246-248 ° C. IR spectrum, cm: v (acid) 1720; (pyrone) 1620. NMR spectrum (SSR) §, ppm relative to TMS: k (s, 3N); 7 (s, 1H); 7.1-8.1 (m, 8H); 12.6 (variable, 1H). Calculated: C 66.83; H 4.01; N 3.71; O 16.96; S 18.50. Found: C 66.73; H 3.95; N 3,66; S 8.56 „ 2- (2-Chlorophenyl) - -oxo-1H- (1) -benzopyran-8-acetic acid. molol 351.35 (compound 117). PFs 173-175 ° C. IR spectrum, cm: V s-o acid 17U; CfcQ (pyrone) t6.o7 NMR spectrum (DMCO) & ppm att. 1739 6 O Found: C 64,72; H 4.85: N 12.04. 2 - (.- Amino-thiazolylphenyl) co-AN- (1) -benzopyran-8-acetic acid. CZOH1404S, mole 378.388 (compound 118). PF IR10 1710 15 20 25 thirty FQ 263-265 ° Co R-spectrum, cm: v (acid) (pyrone) 1620. NMR spectrum (DMSO) §, ppm relative to TMS: (s, 2H); 7-8.2 (m, with 2H variables, 11H); 12.9 (variable, 1H). Calculated D: C 67.05; H 4.75; b 28.21. Found: C, 67.70; H 4.54; About 7.12. 2- (3,5 Dimethoxyphenyl) - -oxo-G (1) -benzopyran-8-acetic acid. supposedly m , 318 (compound 119). PF 26l-263 ° CIf IR spectrum, cm: v (acid) 1720; 0s-0 (pyrone) 1bZO „ NMR spectrum (DMCO) o, ppm relative to TMS: 3.9 (s, 6H); 4 (s, 2H); 6.5-8 (m, 7H); 12.9 (variable, 1H) Calculated D: C 67.05; H 4.74; About 28.21 „ Found: C, 67.20; H 4.540 2- (A-Pyridyl) - -oxo-H- (1) -benzopyran-8-acetic acid. (N04, mol. 281,256 (co-35 dynenium 120). PFa 275-277 ° C. ( IR spectrum, cm: V (acid) J720; (pyrone) 1b.0. 40 NMR spectrum (DMSO +), pp relative to TMS: A (s, 2I); 7.3-8, (m, 8H). Calculated D: C 68,32; H 3.94; N 4.98; About 22.76. 45 Found D: C 67.94; H 4.09; N 5.12. 2- {2-Pyridyl) -A-oxo-I- (1) -benz pyran-8-acetic acid. C (6H (, NO, mol. M. 281,256 (compound 5 AO; n 121). PF $ 221-223 ° C. . IR spectrum, cm: VC.Q (acid) 1720-17 0; (pRonT. NMR spectrum (DMSO) o, ppm relative to TMS: 3.25 (s, 6H) -H (s, 2H); $ 5 linen ° MS: A, l (s / 2I); 7.2 (s, 7 (s, 1H); 7.2-8 (m, 7H); 12.3 (pe- 1HJJ 7.25-9 (m, 8H); 13 (variable 1 H). Calculated,%: C 68,32; H 3.94; N 4.98; About 22.76. belt, 1H). Calculated D: C, 64.95; H 4.88; N 11.96; About 18.22. - Found: C 64,72; H 4.85: N 12.04. 2 - (.- Amino-thiazolylphenyl) co-AN- (1) -benzopyran-8-acetic acid. CZOH1404S, mole 378.388 (compound 118). PF IR10 1710 15 20 25 thirty FQ 263-265 ° Co R-spectrum, cm: v (acid) (pyrone) 1620. NMR spectrum (DMSO) §, ppm relative to TMS: (s, 2H); 7-8.2 (m, with 2H variables, 11H); 12.9 (variable, 1H). Calculated D: C 67.05; H 4.75; b 28.21. Found: C, 67.70; H 4.54; About 7.12. 2- (3,5 Dimethoxyphenyl) - -oxo-H- (1) -benzopyran-8-acetic acid. supposedly m , 318 (compound 119). PF 26l-263 ° CIf IR spectrum, cm: v (acid) 1720; 0s-0 (pyrone) 1bZO „ NMR spectrum (DMCO) o, ppm relative to TMS: 3.9 (s, 6H); 4 (s, 2H); 6.5-8 (m, 7H); 12.9 (variable, 1H). Calculated D: C 67.05; H 4.74; About 28.21 „ Found: C, 67.20; H 4.540 2- (A-Pyridyl) - -oxo-H- (1) -benzopyran-8-acetic acid. (N04, mol. 281,256 (co-35 dynenium 120). PFa 275-277 ° C. ( IR spectrum, cm: V (acid) J720; (pyrone) 1b.0. 40 NMR spectrum (DMSO +), ppm relative to TMS: A (s, 2I); 7.3-8.8 (m, 8H). Calculated D: C 68,32; H 3.94; N 4.98; About 22.76. 45 Found D: C 67.94; H 4.09; N 5.12. 2- {2-Pyridyl) -A-oxo-I- (1) -benzopyran-8-acetic acid. C (6H (, NO, mol. M. 281,256 (Compound 5) 121. PF $ 221-223 ° C. . IR spectrum, cm: VC.Q (acid) 1720-17 0; (pRonT. NMR spectrum (DMSO) o, ppm rela tive to 5 ° MS: A, l (s / 2I); 7.2 (s, 1HJJ 7.25-9 (m, 8H); 13 (variable -41 FoundD: 68.50; H 3.89; N 4.86. 2- (4-Hexylphenyl) -4-oxo-4H- (1) is benzopyran-B-acetic acid. mol.m. 364,422 (compound 122). PFq 154-156 ° C. IR spectrum, cm: 0 (acid) 1720; (pyrone) 1620. I NMR spectrum (DMSO) Ј, rrtp relative to TMS: 0.7-2.8 (m, 13U; 4 (s, 2H); 7 (s, 1H); 7.2-8, 1 (m, 7H; 12.9 (variable, 1H). Calculated% C, 75.80; H 6.64; About 17.56. Found: C 75.50; H 6.49 „ 2 (3-Methylphenyl) -4-oxo-4H- (1H) - benzopyran-8-acetic acid. mol.m. 294,292 (compound 123). PFq 252-254aC, IR spectrum, cm: (acid) 1720; } Ce0 (pyrone) 1620o NMR spectrum (СГ3СООВ) о, ррт relative to TMSg 2.55 (s, 2H); 4.5 (m, 2H); 7.5-8.6 (m, 8H). Calculated,% C 73.46; N 4.80; O 21.75 Found: C, 73.74; H 4.86. 2- (4-Benzoylphenyl) -4-oxo 4H- (1) benzofuran-8-acetic acid mol.m. 384.368 (Compound 124). PFa 257-259 ° С „ IR spectrum, cm-: V (acid) 1720; (benzoyl) 1b5P; - (pyrone) 1620. NMR spectrum (CFoCOOD) §, ppm relative to TMS: 4.5 (s, 2H); 7.5-8.7 (m, 13H). Calculated D: C 74.99; H 4.20; About 20.81, Found,%: C 75.11; H 4.09 2- (4-Undecylphenyl) - -oxo-H- (1) benzopyran-8-acetic acid. CjgHjqO, mol.m. 3,552 (Compound 125). PFq 150-1520C IR spectrum, cm: (acid) 17U; (pyrone) 1620. NMR spectrum () Q, ppm relative to TMS: 0.6-1.6 (m, 23H); , 5 (s, 2H); 7.5-8.4 (m, 8H). Calculated,%: C 77.39; H 7.89; About 14.73. Found,%; C 77.34; H 7.87, 3 (3-Nitro-A-phenylphenyl) -4-oxo-4H- (1) -benzopyran-8-acetic acid. 1739846 42 0 C2iHf5-NO, mol.m. 401,358 (compound 1 26). PFq 270-272 ° C. IR spectrum, O.O (acid) 1720; (pyrone) 1620. NMR spectrum (DMCO) $, ppm relative to TMS: 4 (s, 2H); 7.2-8.7 (m, 12H); 12.9 (variable, 1H). Calculated D: C 68.88; H 3.77; N 3.49; About 23.92o Nickel: C 68.72; H 3.66; N 3.35, 2- (4-Trifluoromethylphenyl) -4-oxo-5 4H- (1) -benzopyran-8-acetic acid. C (8HI1H04 348.268 (compound 127). PFG 216-218 ° C IR spectrum, cm Y: N (acid) 1720; with „0 (pyrone) 164P. NMR spectrum (DMSO), ppm relative to TMS: 4 (s, 2H): 7.1-8.4 (m, 8H); 12.8 (variable, 1H). Calculated D: C 63.07; H 3.18; F 16.37; About 18.38, Found: C 63.02; H 3.32; F 16.37 2- (4-Dimethyltriazenylphenyl) -4-oxy-4H- (1) -benzopyran-8-acetic acid. mol- 351.35 (compound 0 S 0 five m, 7n3 128). PFQ 209-211 ° C. IR spectrum, Vc "o (acid) 1720; (pyrone) 1620. NMR spectrum (DMCO) $, ppm relative to TMS: 3.3 (m, 6H); 4 (s, 2H); 7 (s, 1H); 7.2-8.1 (m, 8H); 12.8 (variable, 1H). 0 Calculated D: C 64.95j H 4.88; N 11.96; About 18.22. Found: C 64,75; H 4.95; N 12.25, 2- (3-Nitro-4-methoxyphenyl) -4-ok- $ co-4H- (1) -benzopyran-8-acetic acid C18H14, N07, mol.m. 355,292 (compound 129). PFq 254-256 ° C. 0 IR spectrum, cm: V (acid) 1720; JC-0 (pyrone) 1620. NMR (): 4.1 (s, 3N); 4.3, (s, 2H); 7.1-9 Cm, 7H). Calculated D: C 60.85; H 3.69; N 3.94; About 31.52. Found: C 61.07; H 3.68; N 4.16. 2- (4-Tetrabutylphenyl) -4-oxo-4H- (1) -benzopyran-8-acetic acid. 31 Smn20P4-. mole „m, 336.37 (compound 130). PFQ 240-242 ° IR spectrum, (acid) 1720; (pyrone) 1byu. NMR spectrum (DMCO) $, rrp relative to TMS: 1.2 (s, 6H); C, 5 (s, 2H); 7.1-3.3 (m, 8H); 12.9 (variable, 1H). Calculated D: C, 74.98; H 5.99; About 19.03. Found: C, 74.76; H 5.85. The compounds of formula (I) have anti-cancer activity, especially against pancreatic cancer, and better threshold characteristics compared to known compounds. In addition, the proposed compounds have immunomodulatory activity, in particular, they stimulate the formation of interferon and killer cells. The compounds inhibit platelet aggregation and prolong bleeding time. Therefore, the compounds are useful in treating cancers, for example pancreatic cancer, and are believed to be useful in suppressing the formation of blood clots. The compounds of formula (I) have interleukin-2 (IL-2) activity. In particular, the compounds of the formula have been found to have in vitro activity against a variety of tumors according to the following method. The test compounds are placed on a paper disk, which is placed in the middle of an agar-agar base on which the culture of the selected tumor is placed. Activity is measured by the growth inhibition test for cultured tumors. Growth is measured as a function in units (1 unit of 25 µm), which are inhibited. These units represent the growth surface of a tumor culture. The product is considered to have a significant level of activity if the number of zones that are inhibited exceeds 250. The tumors used in these tests are a single carcinoma pancreatic ROZ and a C08 column. In tests when tumor ROS was inhibited, compounds 19, 58, and 70 when 1000 μg were applied to the disk, followed by 333 6 shown inhibition values of 900, 350 and 00, respectively. In the case of an SP8 tumor, compounds 31, 19 and 70, applied in an amount of 1000 µg per disk, show inhibition values of 500, 50 and 500, respectively. In addition, the compounds of formula (I) tested in studies on JQ animals showed a threshold level, i.e. the ratio between activity and toxicity, which provides therapeutic safety, is higher than, in particular, flavin-8-acetic acid. For example, flavin-8-acetic acid, in a group of 10 mice administered in a dose of DOO mg / kg, provides a lethal dose to 10 mice out of 10 in a test of 20 Res 20 days. Compound 31 gives only 6 of 10 deaths with its introduction in the amount of 00 mg / kg after 20 days. Compound 29 provides 1 death out of 10 at a dose of 00 mg / kg 25 after 20 days, and compound 58 does not result in death in a group of 10 mice at a dose of 00 mg / kg after 20 days. The compounds of formula (I) possess immunomodulatory properties, as well as high activity for the immune system, in particular, they stimulate the activity of killer cells and induce the formation of interferon (INF). 35 Stimulation of killer cell activity. The determination of killer cell activity was carried out in accordance 40 with the following methodology. BAZ B / C mice were injected intravenously with 0.25 ml HB SS or 200 mg / kg of the compound of formula (I). Two hours after the compound is administered, the spleen of the animal is ground to 45 of the suspension, Lebris and the cell remains are removed by sedimentation and the red cells are lysed with distilled water. The resulting cell suspension is then filtered through 50 sterile filter and washed twice with HB SS. Different numbers of spleen cells are incubated with 1 10 UAS-1 type tumor cells stained 55 chromium 51. The duration of the incubation is kh at 370C in medium type RPM1 with an additional 5% FBS, penicillin (100 and / ml), steptomycin (100 μg / ml), Z-glutamine (20 ml), 1151 sodium pyruvate (1 mM), non-essential amino acids (0.1 mM) in a buffer medium. The floating bodies are removed and counted. Results are expressed in lytic units of UZW, where is the quantity required for the lysis of 1-10 target cells. For example, it was found that connection 19 provides 80 UZ, connections 25 - 60 UZ, connection 2 - 110 UZ. And control animals treated with HBSS do not show activity, measured in lytic units (UZ). Induction of interferon. 0.25 ml of HBSS or 200 mg / kg of the formula (I) compound was intravenously injected into BAZB / C mice. Interferon-i activity is determined using viral vesicular stomatitis method. A unit of XIFN with the amount of IFN in 1 ml of the sample required to reduce the urine count by 50%. For example, it was found that compounds 19, 25, and 67 had an activity of 1000 units of IFN, then, as control animals treated with HBSS, showed no induction when receiving IFN. Regarding the inhibition of the ROZ tumor, additional data showed that compounds 8.42, 63 and 116 had the same level of effectiveness as compounds 19.58 and 70. With regard to in vitro activity, the results of the compounds of formula (I) over known ones show the results , obtained on adenocarcinoma of the pancreatic duct in a mouse: when 2x160 mg / kg was administered in vitro, compounds 8 and 116 had T / C 0. life R, O where X is oxygen or sulfur; RJ is phenyl, unsubstituted or substituted for N substituted by the lL.1 group, R2 is hydrogen or hydroxy, characterized in that the compound R7 0 20 / have indicated where X, R and R2 meanings is reacted with a cyanide derivative, for example tetraethyl ammonium cyanide or potassium cyanide, 1 in an organic solvent, such as chloroform or dichloethane, at a temperature of 20-120 C for an hour and the resulting cyanide of the formula
权利要求:
Claims (1) [1] Invention Formula The method of obtaining the flavonoid derivatives of the general formula where X, R and R have the indicated meanings, hydrolyzed with hydrochloric or sulfuric acid in a mixture of acetic acid - water at boiling for -8 hours.
类似技术:
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同族专利:
公开号 | 公开日 DE68911742T2|1994-04-28| AU630345B2|1992-10-29| EP0341104A2|1989-11-08| DK166789A|1989-10-07| IN170909B|1992-06-13| PT90214B|1994-07-29| HUT49600A|1989-10-30| EP0341104A3|1989-11-29| NO172344B|1993-03-29| IL89840A|1996-10-31| NZ228625A|1992-03-26| CA1325205C|1993-12-14| PT90214A|1989-11-10| NO172344C|1993-07-07| YU47308B|1995-01-31| ZA892523B|1990-05-30| DE68911742D1|1994-02-10| OA09036A|1991-03-31| JPH026473A|1990-01-10| AU3250589A|1989-10-12| IE62858B1|1995-03-08| DK166789D0|1989-04-06| NO891415D0|1989-04-05| ES2060799T3|1994-12-01| NO891415L|1989-10-09| EP0341104B1|1993-12-29| IL89840D0|1989-12-15| YU69289A|1991-06-30| IE891087L|1989-10-06| AT99302T|1994-01-15| HU206701B|1992-12-28| MA21528A1|1989-12-31|
引用文献:
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