Aminotriazolopyridine derivatives as adenosine receptor ligands

专利摘要:
The present invention relates to formula (I) wherein R 1 is lower alkoxy, cycloalkyl or aryl unsubstituted or substituted with halogen or lower alkoxy, or -NR'R "where R 'and R" are independently of each other hydrogen, or Lower alkyl, lower alkenyl, lower alkynyl or-(CR 2 ) n -aryl substituted or unsubstituted with one to three substituents selected from the group consisting of halogen or lower alkoxy, or-(CH 2 ) n + 1 NR 2 ,-(CH 2 ) n -pyridinyl,-(CH 2 ) n -indanyl,-(CH 2 ) n -cycloalkyl,-(CH 2 ) n -O-lower alkyl,-(CH 2 ) n -C (O) -NR 2 ,-(CH 2 ) n -CF 3, or R 'and R "together with the N atom attached to them are pyrrolidin-1-yl, piperidin-1-yl, 3,4-dihydro-1H-isoquinolin-2-yl, morpholinyl, azatidin-1-yl, 3,6-dihydro-2H-pyridin-1-yl, thiomorpholinyl, 2,5 -Dihydro-pyrrole-1-yl, thiazolidin-3-yl, piperazinyl, azocan-1-yl, azepan-1-yl, octahi Form quinolin-1-yl, octahydroquinolin-2-yl, 1,3,4,9-tetrahydro-b-carboline-2-yl, the ring being lower alkyl, phenyl, benzyl, pyridyl Can be unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of -C (O) -NR 2 ,-(CH 2 ) n -O-lower alkyl or -NR-C (O) -lower alkyl. R 2 is aryl or a 5 or 6 membered heteroaryl group, the ring is unsubstituted or substituted with lower alkyl, halogen, hydroxy or lower alkoxy; X is a bond or -N (R) CH 2- R is hydrogen or lower alkyl; n is 0, 1, 2, 3, 4, 5, or 6) and a pharmaceutically acceptable salt thereof, which compounds have a good affinity for adenosine receptors. As such, it can be used to treat diseases associated with the receptor.
公开号:KR20030061446A
申请号:KR10-2003-7008004
申请日:2001-12-07
公开日:2003-07-18
发明作者:브로드벡베른트；네테코벤마티아스하인리히
申请人:에프. 호프만-라 로슈 아게；
IPC主号:

专利说明:

Aminotriazolopyridine derivatives as adenosine receptor ligands {AMINOTRIAZOLOPYRIDINE DERIVATIVES AS ADENOSINE RECEPTOR LIGANDS}
[10] Adenosine regulates a wide range of physiological functions by interacting with specific cell surface receptors. The possibility of adenosine receptors as drug targets was first reported in 1982. Adenosine includes bioactive nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and cyclic adenosine monophosphate (cAMP); And structurally and metabolically related to the biochemical methylating agent S-adenosyl-L-methion (SAM); Coenzyme NAD, FAD and coenzyme A; And structurally related to RNA. These related compounds along with adenosine are important in the regulation of numerous aspects of cellular metabolism and the regulation of different central nervous system activities.
[11] Adenosine receptors have been classified into A ₁ , A _2A , A _2B and A ₃ receptors belonging to the class of G-protein-binding receptors. Activation of adenosine receptors by adenosine initiates a signal transduction mechanism. This mechanism is dependent on receptor related G protein. Each adenosine receptor subtype is typically characterized by an adenylate cyclase agonist and uses cAMP as the second messenger. A ₁ and A ₃ receptors bound to G _i proteins inhibit adenylate cyclase to reduce the amount of cAMP in the cell, while A _2A and A _2B receptors bound to G _s proteins bind adenylate cyclase Activation increases the amount of cAMP in the cell. A ₁ receptor systems are known to include activation of phospholipase C and regulation of potassium and calcium ion channels. The A ₃ subtype, besides being associated with adenylate cyclase, also stimulates phospholipase C to activate calcium ion channels.
[12] The A ₁ receptor (326-328 amino acids) was cloned from various species (Kanein, Human, Rat, Dog, Cheek, Bouvine, Guinea Pig) with 90-95% sequence identity among mammalian species. A _2A receptors (amino acids 409-412) were cloned from canine, rat, human, guinea pig and mouse. The A _2B receptor (332rd amino acid) was cloned from humans and mice having 45% homology with the human A _2B receptor, including human A ₁ and A _2A receptors. A ₃ receptor (317-320 amino acids) was cloned from human, rat, dog, rabbit and sheep.
[13] The A ₁ and A _2A receptor subtypes have been proposed to play a complementary role in the adenosine regulation of energy supply. Adenosine, a metabolic product of ATP, diffuses from cells and acts locally to activate adenosine receptors to reduce oxygen demand (A ₁ ) or increase oxygen supply (A _2A ), thereby balancing tissue energy supply with demand To recover. The function of both subtypes is to increase the amount of oxygen available to tissues and to protect the cells against damage caused by short-term oxygen imbalance. One important function of endogenous adenosine is to prevent damage during trauma such as hypoxia, ischemia, hypotension and seizure activity.
[14] In addition, adenosine receptor agonists bind to mast cells expressing the rat A ₃ receptor to increase inositol triphosphate and intracellular calcium concentrations, which are known to allow antigen-induced secretion of inflammatory mediators. Thus, A ₃ receptors play a role in mediating asthma attacks and other allergic reactions.
[15] Adenosine is also a neuromodulator of broad importance in regulating the molecular mechanisms underlying many aspects of physiological brain function by mediating central inhibitory action. Increased neurotransmitter release is accompanied by trauma such as hypoxia, ischemia and seizures. These neurotransmitters ultimately lead to neurodegeneration and neuronal death leading to brain damage or brain death in the individual. Thus, adenosine A ₁ agonists that act similarly to the central inhibitory action of adenosine may be useful as neuroprotective agents. Adenosine has been proposed as an endogenous anticonvulsant that inhibits the release of glutamate from excitatory neurons and inhibits neuronal firing. Thus, adenosine agonists can be used as therapeutic agents for epilepsy. Adenosine antagonists have been shown to stimulate the activity of the CNS and to be effective as cognitive enhancers. Selective A _2a antagonists have therapeutic potential in the treatment of various forms of dementia, such as Alzheimer's disease, and are useful as neuroprotective agents. Adenosine A ₂ receptor antagonists inhibit Parkinson's syndrome by inhibiting the release of dopamine from the central synaptic terminus and reducing motor activity. Adenosine's main activity is also related to the molecular mechanisms underlying sedation, hypnosis, schizophrenia, anxiety, pain, respiration, depression and substance abuse. Thus, drugs that act on adenosine receptors also have therapeutic potential as sedatives, muscle relaxants, antipsychotics, anxiolytics, analgesics, respiratory stimulants and antidepressants.
[16] An important role of adenosine in the cardiovascular system is as a cardioprotectant. The amount of endogenous adenosine increases in response to ischemia and hypoxia and protects cardiac tissue during and after trauma (preconditioning). As such, adenosine agonists have the potential as cardioprotectants.
[17] Adenosine regulates renal function in many aspects, including renin release, glomerular filtration rate, and renal blood flow. Compounds that antagonize the renal action of adenosine have the potential as kidney protectors. Adenosine A ₃ and / or A _2B antagonists may also be useful for the treatment of asthma and other allergic reactions.
[18] Numerous documents describe the current known content of adenosine receptors and include, for example, the following publications: Bioorganic & Medicinal Chemistry, 6, (1998), 619-641; Bioorganic & Medicinal Chemistry, 6, (1998), 707-719; J. Med. Chem., (1998), 41, 2835-2845; J. Med. Chem., (1998), 41, 3186-3201; J. Med. Chem., (1998), 41, 2126-2133; J. Med. Chem., (1999), 42, 706-721; J. Med. Chem., (1996), 39, 1164-1171; Arch. Pharm. Med. Chem., (1999), 332, 39-41.
[1] The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof:
[2]
[3] Where
[4] R ¹ is lower alkoxy, cycloalkyl or aryl unsubstituted or substituted with halogen or lower alkoxy, or —NR′R ″ (wherein R ′ and R ″ independently of one another is hydrogen or in the crowd consisting of halogen or lower alkoxy) Lower alkyl, lower alkenyl, lower alkynyl or-(CR ₂ ) _n -aryl unsubstituted or substituted with one to three substituents selected, or-(CH ₂ ) _{n + 1} NR ₂ ,-(CH ₂ ) _n -Pyridinyl,-(CH ₂ ) _n -indanyl,-(CH ₂ ) _n -cycloalkyl,-(CH ₂ ) _n -O-lower alkyl,-(CH ₂ ) _n -C (O) -NR ₂ Or-(CH ₂ ) _n -CF ₃ or R 'and R "together with the N atom attached to them are pyrrolidin-1-yl, piperidin-1-yl, 3,4-dihydro-1H Isoquinolin-2-yl, morpholinyl, azatidin-1-yl, 3,6-dihydro-2H-pyridin-1-yl, thiomorpholinyl, 2,5-dihydro-pyrrole-1- Yl, thiazolidin-3-yl, piperazinyl, azocan-1-yl, azepan-1-yl, octahydroquinolin-1-yl, octahydr Quinolin-2-yl, 1,3,4,9- tetrahydro--b- car Boleyn form a 2-yl, and the ring is lower alkyl, phenyl, benzyl, pyridyl, -C (O) -NR ₂ ,-(CH ₂ ) _n -O-lower alkyl or -NR-C (O) -lower alkyl may be substituted or unsubstituted with 1 to 3 substituents selected from the group consisting of;
[5] R ² is aryl or a 5 or 6 membered heteroaryl group, said ring being unsubstituted or substituted with lower alkyl, halogen, hydroxy or lower alkoxy;
[6] X is a bond or -N (R) CH _2- ;
[7] R is hydrogen or lower alkyl;
[8] n is 0, 1, 2, 3, 4, 5 or 6.
[9] It has surprisingly been found that compounds of formula I are adenosine receptor ligands.
[19] It is an object of the present invention to provide a compound of formula (I) as a pharmaceutically active substance and a pharmaceutically acceptable salt thereof, a process for their preparation, a medicament based on the compound according to the invention and a process for its preparation, as well as adenosine systems In the suppression or prevention of control-based diseases (e.g., Alzheimer's disease, Parkinson's disease, neuroprotection, psychosis, anxiety, pain, respiratory deficiency, depression, asthma, allergic reactions, hypoxia, ischemia, seizures and substance abuse) Use of compounds of formula (I). In addition, the compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, epileptics, anticonvulsants and cardioprotectants. The most preferred indications according to the invention are the treatment or prevention of certain depressive disorders, neuroprotection and Parkinson's disease, for example, based on A _2A receptor antagonist activity and including central nervous system diseases.
[20] As used herein, the term "lower alkyl" refers to saturated straight or branched chain alkyl groups containing 1 to 6 carbon atoms, for example methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, 2-butyl, t-butyl and the like. Preferred lower alkyl groups are groups having from 1 to 4 carbon atoms.
[21] The term "lower alkenyl" as used herein refers to unsaturated straight or branched chains containing 2 to 6 carbon atoms and at least one double bond, for example ethylene, propylene, isopropylene, n-butylene, i-butyl Lene, 2-butylene, t-butylene and the like. Preferred lower alkenyl groups are groups having 2 to 4 carbon atoms.
[22] As used herein, the term "lower alkynyl" refers to an unsaturated straight or branched chain containing 2 to 6 carbon atoms and one or more triple bonds.
[23] The term "cycloalkyl" means a saturated carbocyclic group containing 3 to 8 carbon atoms.
[24] The term "halogen" means chlorine, iodine, fluorine and bromine.
[25] The term "lower alkoxy" means a group wherein the alkyl moiety is as defined above and attached via an oxygen atom.
[26] The term "5- or 6-membered heteroaryl group" means, for example, furanyl, thiophenyl, pyrrolyl, thiazolyl or pyridinyl.
[27] The term "aryl" means phenyl or naphthyl.
[28] The term "pharmaceutically acceptable acid addition salts" refers to inorganic acids such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methane-sulfonic acid, p-toluenesulfonic acid, and the like; Salts formed with organic acids.
[29] Preferred are compounds of formula I, wherein X is a bond.
[30] For example, R ¹ is —NR′R ″ wherein R ′ and R ″ are independently of each other lower alkyl, lower alkenyl, lower alkynyl, — (CH ₂ ) _n —C (O) —N (CH ₃ ) ₂ ,-(CH ₂ ) _n -OCH ₃ ,-(CH ₂ ) _n -cycloalkyl or-(CH ₂ ) _n -pyridin-2-yl), and R ² is substituted or unsubstituted with halogen or lower alkyl; Preference is given to compounds of the formula (I) which are ringed furyl or thiophenyl.
[31] Examples of such compounds are as follows:
[32] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide,
[33] 5-amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide,
[34] 5-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide,
[35] 5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide,
[36] (5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl metanon,
[37] 5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide,
[38] 5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide,
[39] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-methyl-amide,
[40] 5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-prop-2-ynyl-amide ,
[41] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-methyl-amide,
[42] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide,
[43] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid isopropyl-methyl-amide,
[44] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-methyl-amide,
[45] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide,
[46] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diallylamide,
[47] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisopropylamide,
[48] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-ethyl-amide,
[49] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-pentyl-amide,
[50] 5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (2-dimethylamino-ethyl) -methyl -amides,
[51] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylmethyl-propyl-amide,
[52] 5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl- (2-pyridin-2-yl -Ethyl) -amide,
[53] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dipropylamide,
[54] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide,
[55] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-cyclopentyl-amide,
[56] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide,
[57] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisobutylamide,
[58] 5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-pyridin-2-yl -Ethyl) -amide,
[59] 1- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -piperidine- 3-carboxylic acid diethylamide,
[60] 5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dimethylcarbamoylmethyl-methyl-amide,
[61] 5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (2-methoxy-ethyl) -methyl -Amide or
[62] 5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-methoxy-ethyl) -amides.
[63] R ¹ is —NR′R ″ wherein R ′ and R ″ are independently of each other lower alkyl, lower alkenyl, lower alkynyl,-(CH ₂ ) _n -phenyl or-(CH ₂ ) _n -pyridinyl Is also preferred, wherein R ² is thiazolyl.
[64] Examples of such compounds are as follows:
[65] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide,
[66] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide,
[67] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-methyl-amide,
[68] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-prop-2-ynyl-amide,
[69] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-methyl-amide,
[70] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide,
[71] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid isopropyl-methyl-amide,
[72] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-methyl-amide,
[73] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-pyridin-4-ylmethyl-amide,
[74] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dibenzylamide,
[75] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethylamide,
[76] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dipropylamide or
[77] 5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisobutylamide.
[78] R ¹ is —NR′R ″ wherein R ′ and R ″ together with the N atom attached to them are pyrrolidinyl, piperidinyl, morpholinyl, 3,6-dihydro-2H-pyridine-1- 1,2,5-dihydro-pyrrole-1-yl, azocan-1-yl, the ring being lower alkyl, lower alkoxy, -C (O) -NH ₂ , -C (O) N ( Preference is given to compounds of the formula I in which CH ₃ ) ₂ , -N (CH ₃ ) -C (O) -CH ₃ may be unsubstituted or substituted, and R ² is substituted or unsubstituted furyl.
[79] Examples of such compounds are as follows:
[80] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl -Methanone,
[81] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl -Methanone,
[82] (5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone,
[83] (5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone,
[84] (5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -morpholin-4-yl-methanone,
[85] [5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,6-dihydro- 2H-pyridin-1-yl) -methanone,
[86] [5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-pyrrolidine -1-yl) -methanone,
[87] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dihydro -Pyrrole-1-yl) -methanone,
[88] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-pyrroli Din-1-yl) -methanone,
[89] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dimethyl- 2,5-dihydro-pyrrol-1-yl) -methanone,
[90] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dimethyl- Pyrrolidin-1-yl) -methanone,
[91] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,6-dimethyl- Morpholin-4-yl) -methanone,
[92] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-piperi Din-1-yl) -methanone,
[93] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-methyl-piperi Din-1-yl) -methanone,
[94] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -azokan-1-yl- Methanone,
[95] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,5-dimethyl- Piperidin-1-yl) -methanone,
[96] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-[(2R, 5R)- Trans-2,5-dimethyl-pyrrolidin-1-yl] -methanone,
[97] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(cis-2,6- Dimethyl-morpholin-4-yl) -methanone,
[98] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(S-2-methoxy Methyl-pyrrolidin-1-yl) -methanone,
[99] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(R-2-methoxy Methyl-pyrrolidin-1-yl) -methanone,
[100] 1- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -L-pyrroli Din-2-carboxylic acid amide,
[101] 1- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -D-pyrroli Din-2-carboxylic acid amide,
[102] 1- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -pyrrolidine- 2-carboxylic acid dimethylamide,
[103] N- {1- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -pi Ralidin-3-yl} -N-methyl-acetamide,
[104] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(5-ethyl-2- Methyl-piperidin-1-yl) -methanone or
[105] 1- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -piperidine- 3-carboxylic acid amide.
[106] R ¹ is —NR′R ″ wherein R ′ and R ″ together with the N atom attached to them are pyrrolidinyl, piperidinyl, octahydroquinolin-1-yl, 2,5-dihydro-pyrrole- 1-yl, thiazolidinyl, thiazolyl, azepan-1-yl or azocan-1-yl, the ring may be substituted or unsubstituted with lower alkyl, and R ² is thiazolyl Also preferred are compounds of formula I, for example the following compounds:
[107] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone,
[108] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone,
[109] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,5-dihydro-pyrrol-1-yl ) -Methanone,
[110] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-pyrrolidin-1-yl) -Methanone,
[111] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -thiazolidin-3-yl-methanone,
[112] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azpan-1-yl-methanone,
[113] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl) -Methanone,
[114] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(4-methyl-piperidin-1-yl) -Methanone,
[115] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azokane-1-yl-methanone,
[116] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3,5-dimethyl-piperidine-1- Sun,
[117] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,6-dimethyl-piperidine-1- Sun,
[118] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(cis-2,6-dimethyl-piperidine- 1-day) -methanone or
[119] (5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(octahydro-quinolin-1-yl) -methanone .
[120] In addition, R ¹ is —NR′R ″ wherein R ′ and R ″ together with the N atoms attached to them are pyrrolidin-1-yl, azepan-1-yl, piperidin-1-yl, Preference is given to compounds of the formula (I) which form azocan-1-yl, wherein the ring may be substituted or unsubstituted with lower alkyl, lower alkoxy) and R ² is pyridyl.
[121] Examples of such compounds are as follows:
[122] (5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-pyrrolidin-1-yl)- Methanone,
[123] (5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azpan-1-yl-methanone,
[124] (5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl)- Methanone,
[125] (5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl)- Methanone,
[126] (5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azokane-1-yl-methanone,
[127] (5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3,5-dimethyl-piperidin-1-yl ) -Metanon or
[128] (5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -R-2-methoxymethyl-pyrrolidine-1- Th) -metanon.
[129] In addition, R ¹ is -NR'R "wherein R 'and R" are independently of each other lower alkenyl, lower alkyl,-(CH ₂ ) _n -cycloalkyl,-(CH ₂ ) _n -pyridinyl or- Preferred are compounds of formula I, _wherein (CH ₂ ) _n -phenyl and R ² is pyridyl, for example the following compounds:
[130] 5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diallylamide,
[131] 5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylmethyl-propyl-amide,
[132] 5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-cyclopentyl-amide,
[133] 5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-pyridin-4-yl-methyl-amide,
[134] 5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide or
[135] 5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dibenzylamide.
[136] Further, of Formula I, X is -N (R) CH _2- , R ¹ is cycloalkyl or aryl unsubstituted or substituted with halogen, and R ² is furyl or thiazolyl unsubstituted or substituted with halogen or methyl. Compound is preferred.
[137] The compounds of formula (I) and pharmaceutically acceptable salts thereof of the present invention are prepared by methods known in the art, for example a) by reacting a compound of formula (I-1) with a compound of formula (II) Or b) reacting a compound of formula III with a compound of formula V in the presence of a compound of formula IV to give a compound of formula I-3, or c) a compound of formula VI is HCl, a compound of formula IV and Reacting with a compound of V in sequence to give a compound of formula (I-4), or d) modifying one or more substituents R ¹ or R ² within the definitions given above and, if necessary, adding the pharmaceutically acceptable acid It may be prepared by a method comprising converting to a salt:
[138]
[139] HNR'R "
[140]
[141]
[142]
[143] R ² CHO
[144]
[145]
[146]
[147] Where
[148] R ¹ , R ² , R 'and R "are as defined above.
[149] Examples 1 to 435 and Schemes 1 and 2 below describe the preparation of the compounds of formula (I) in more detail.
[150]
[151] Scheme 1 illustrates a method for preparing 2,6-diamino-isonicotinic acid methyl ester (X), which is a starting material in another method for obtaining a compound of formula (I). According to Scheme 1, 2,6-dichloroisonicotinic acid (commercially available product, VIII) is mixed with copper powder in aqueous ammonia and the mixture is heated in an autoclave for about 12 hours. After cooling to room temperature, the copper is filtered off and the filtrate is treated with HCl to bring pH = 5. The 2,6-diamino-isonicotinic acid (IX) obtained is dissolved in methanol and treated with aqueous HCl at 0 ° C. The mixture is concentrated, dissolved in water and brought to pH = 8 by addition of saturated NaHCO ₃ . 2,6-Diamino-isonicotinic acid methyl ester (X) is obtained after extraction with ethyl acetate.
[152]
[153] Wherein the substituents R ¹ and R ² have the meanings given above.
[154] According to Scheme 2, the compounds of formulas I-1, I-2, I-3 and I-4 are obtained. Compound (I-1) of formula (I), wherein R ¹ is methoxy, may be prepared as follows. To a solution of 2,6-diamino-isonicotinic acid methyl ester (X) in dioxane is added O-mesitylenesulfonylhydroxylamine (IV) and the corresponding aldehyde (V). The mixture is stirred at about 100 ° C. for several hours. After addition of a KOH solution in methanol, the solution is stirred at room temperature and then the product is concentrated.
[155] The obtained compound of formula (I-1) can be further modified with a compound of formula (I-2). Trimethylaluminum or methylaluminoxane is added to a solution of the compound of formula II in dioxane and stirred at room temperature for about 1 hour. Then a mixture of the compound of formula I-1 in dioxane is added and the mixture is heated at about 80 ° C. for 72 hours. After addition of HCl, the compound of formula I-2 is obtained.
[156] Compounds of formula I-3 can be prepared as follows. A solution of 2,6-diamino-isonicotinic acid methyl ester (X) is treated with gaseous ammonia for 1 hour. The mixture is heated in an autoclave at about 60 ° C. for 36 hours and then filtered through decalite. The 2,6-diamino-isonicotinamide obtained is suspended in THF and borane-dimethylsulfide-complex (or NaBH ₄ ) is added. The mixture is refluxed for 4 days. After cooling to room temperature, HCl is added and the mixture is neutralized with NaOH to afford 4-aminomethyl-pyridine-2,6-diamine. The solution of this compound in pyridine is treated with a compound of formula XII together with a catalytic amount of 4-dimethylaminopyridine and stirred at room temperature for 2.5 hours to afford the compound of formula III. To the obtained solution of the compound of formula III in dioxane is also added O-mesitylenesulfonylhydroxylamine, followed by the aldehyde of formula V. The mixture is heated to about 100 ° C. and after 2.5 h KOH in methanol is added. After the mixture is stirred at room temperature, the compound of formula I-3 is obtained.
[157] Compounds of formula (I-4) may be prepared as follows. The mixture of 2,6-diamino-isonicotinic acid methyl ester (X), pyridine and acetic anhydride is stirred at room temperature for 1 hour and then at about 80 ° C. for 1 hour. After purification, the prepared 2,6-bis-acetylamino-isonicotinic acid methyl ester is dissolved in pyridine, slowly added to a mixture of N, O-dimethylhydroxyamide and trimethylaluminum in toluene and stirred at room temperature. After purification, the compound of formula XIII is obtained. In addition, in a solution of 2,6-bis-acetylamino-N-methoxy-N-methyl isonicotinamide (XIII) at room temperature, a compound of the formula R ¹ MgBR in THF, for example 4-fluorophenylmagnesium bromide Add solution. The solution is stirred at room temperature and then at about 40 ° C. for 2 hours. After cooling to room temperature, HCl is added and the mixture is evaporated to dryness. After purification, the compound of formula VI is obtained. This compound is dissolved in dioxane and O-mesitylenesulfonylhydroxylamine and a compound of formula V are added, for example 5-bromo-2-furaldehyde. The mixture is stirred at about 80 ° C. for 30 minutes, KOH is added and the mixture is stirred at room temperature for several hours. After the mixture is purified, the compound of formula I-4 is obtained.
[158] Salt formation is carried out at room temperature according to methods known per se and familiar to those skilled in the art. Salts formed with organic acids as well as salts formed with inorganic acids are contemplated. Hydrochloride, hydrobromide, sulfate, nitrate, citrate, acetate, maleate, succinate, methane-sulfonate, p-toluenesulfonate and the like are examples of such salts.
[159] Compounds of formula (I) and their pharmaceutically available addition salts have useful pharmacological properties. In particular, it has been found that the compounds of the present invention are adenosine receptor ligands.
[160] The compound was then investigated according to the test given.
[161] Human adenosine A _2AReceptor
[162] Human adenosine A _2A receptor was recombinantly expressed in Chinese hamster ovary (CHO) cells using a semliki forest virus expression system. Cells were harvested, washed twice by centrifugation, homogenized and again washed by centrifugation. Finally washed membrane pellets were suspended in Tris (50 mM) buffer (Buffer A) containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl ₂ and 10 mM MgCl ₂ (pH 7.4). [ ³ H] -SCH-58261 (Dionisotti et al ., Br. J. Pharmacol. 121, 353, 1997) binding assay was performed with 2.5 μg of membrane protein, 0.5 mg in 200 μL of Buffer A. Was performed in 96-well plates in the presence of Ysi-poly-L-lysine SPA beads and 0.1 U adenosine deaminoase. Nonspecific binding was defined using xanthine amine homologous species (XAC; 2 μΜ). Compounds were tested at 10 concentrations between 10 μM and 0.3 nM. All assays were performed in duplicate and repeated at least twice. Assay plates were incubated for 1 hour at room temperature before centrifugation, and the bound ligands were measured using a Packard Topcount scintillation counter. IC ₅₀ values were calculated using a nonlinear curve matching program and Ki values were calculated using the Cheng-Prussoff equation.
[163] According to the invention, compounds of formula I have been shown to have a high affinity for the A _2A receptor. Specific values of the compounds prepared in the table below are listed.
[164] Compounds of formula (I) and pharmaceutically acceptable salts of compounds of formula (I) can be used as medicaments, for example in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, for example in the form of tablets, coated tablets, dragees, hard or soft gelatin capsules, solutions, emulsions or suspensions. However, the administration may also be administered parenterally, for example in the form of suppositories, for example in the form of injection solutions.
[165] The compounds of formula (I) may comprise inorganic or organic carriers which are pharmaceutically inert in the preparation of pharmaceutical preparations. Carriers for tablets, coated tablets, dragees and hard gelatin capsules can be used, such as lactose, corn starch or derivatives thereof, talc, stearic acid or its salts and the like. Suitable carriers for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semisolid or liquid polyols and the like. Depending on the nature of the active substance, a carrier may not be necessary at all, but is generally necessary in the case of soft gelatin capsules. Suitable carriers for the production of solutions and syrups are, for example, water, polyols, glycerol, vegetable oils and the like. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semisolid or liquid polyols and the like.
[166] In addition, the pharmaceutical preparations may also contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, odorants, salts for controlling osmotic pressure, buffers, masking agents or antioxidants. It may also contain other therapeutically valuable substances.
[167] Agents containing a compound of formula (I) or a pharmaceutically acceptable salt thereof and a therapeutically inert carrier are also objects of the present invention and include one or more compounds of formula (I) and / or pharmaceutically acceptable acid addition salts, and where necessary The same is true for the preparation of a medicament comprising making one or more other therapeutically useful substances into a herbal dosage form with one or more therapeutically inert carriers.
[168] According to the present invention, the compounds of formula (I) and their pharmaceutically acceptable salts are suitable for diseases based on adenosine receptor antagonistic activity, such as Alzheimer's disease, Parkinson's disease, neuroprotection, schizophrenia, anxiety, pain, respiratory deficiency, depression, It is useful for inhibiting or preventing asthma, allergic reactions, hypoxia, ischemia, seizures and substance abuse. In addition, the compounds of the present invention may be useful as sedatives, muscle relaxants, antipsychotics, epileptics, anticonvulsants and cardioprotectants and in the preparation of corresponding medicaments.
[169] The most preferred indications in the present invention are the treatment or prevention of, for example, certain depression, neuroprotection and Parkinson's disease, including central nervous system diseases.
[170] The dosage may vary within wide limits, but in each particular case it will have to be adjusted to the requirements of the individual. For oral administration, the dosage for adults will vary within about 0.01 mg to about 1000 mg of the compound of formula (I) or the corresponding amount of pharmaceutically acceptable salt of said compound per day. The daily dose may be administered as a single dose or in divided dose forms and may also exceed the above upper limit when instructed.
[171] Tablet Formulation (Wet Granulation)
[172] subject ingredient Mg per tablet 5mg 25mg 100mg 500mg One. Compound of formula (I) 5 25 100 500 2. Lactose Anhydrous DTG 125 105 30 150 3. Sta-Rx 1500 6 6 6 30 4. Microcrystalline cellulose 30 30 30 150 5. Magnesium stearate One One One One gun 167 167 167 831
[173] Manufacturing process
[174] 1. Mix items 1, 2, 3 and 4 and granulate with purified water.
[175] 2. Dry the granules at 50 ° C.
[176] 3. Pass the granules through a suitable grinding device.
[177] 4. Add item 5, mix for 3 minutes and compress under suitable pressure.
[178] Capsule Formulation
[179] subject ingredient Mg per capsule 5mg 25mg 100mg 500mg One. Compound of formula (I) 5 25 100 500 2. Hydration Lactose 159 123 148 --- 3. Corn starch 25 35 40 70 4. talc 10 15 10 25 5. Magnesium stearate One 2 2 5 gun 200 200 300 600
[180] Manufacturing process
[181] 1. Mix items 1, 2 and 3 in a suitable mixer for 30 minutes.
[182] 2. Add items 4 and 5 and mix for 3 minutes.
[183] 3. Fill it into a suitable capsule.
[184] Example 1
[185] 2,6-diamino-isonicotinic acid
[186] A mixture of 20 g (0.1 mol) of 2,6-dichloro isnicotinic acid and 2 g (30 mmol) of copper powder in 300 ml of aqueous ammonia (about 30%) was heated to 180 ° C. in an autoclave (20 bar) for 12 hours. After cooling to room temperature, copper was filtered off and the filtrate was treated with 1N HCl to pH = 5. The precipitate was filtered off and repeatedly dissolved in aqueous ammonia (25%) and subsequently purified by charging with 1N HCl. Filtration and drying in HV gave 13.2 g (83%) of 2,6-diamino-isonicotinic acid as a brown solid.
[187] 1-H-NMR (400 MHz, DMSO-d 6): δ = 7.23 (s, br, 1H, COOH), 6.10 (s, 2H, Ar-H), 5.64 (s, br, 4H, NH ₂ ).
[188] MS m / e (%): 153 (M + H ⁺ , 100).
[189] Example 2
[190] 2,6-diamino-isonicotinic acid methyl ester
[191] A suspension of 11 g (70 mmol) of 2,6-diamino-isonicotinic acid in 270 ml of methanol was treated with gaseous HCl at 0 ° C. for 2 hours. The mixture was concentrated and the residue was dissolved in water and brought to pH = 8 by addition of saturated NaHCO ₃ . Extraction was complete with ethyl acetate and the combined organic phases were dried over MgSO ₄ and the volatiles were removed to yield 9.3 g (77%) of 2,6-diamino-isonicotinic acid methyl ester as a yellow solid.
[192] 1-H-NMR (400 MHz, DMSO-d 6): δ = 6.11 (s, 2H, Ar-H), 5.69 (s, 4H, NH ₂ ), 3.77 (s, 3H, CH ₃ ).
[193] MS m / e (%): 167 (M + H ⁺ , 100).
[194] Elemental Analysis: Calculated C 50.30, H 5.43, N 25.14, found C 50.27, H 5.26, N 24.11.
[195] Example 3 (General Method)
[196] 5-amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester
[197] To a solution of 1 g (5.98 mmol) of 2,6-diamino-isonicotinic acid methyl ether in 50 ml dioxane, 1.41 g (6.58 mmol, 1.1 equivalents) of O-mesitylenesulfonylhydroxylamine and 2 hours at room temperature Then 0.824 g (7.77 mmol, 1.3 equiv) of benzaldehyde was added and stirred at 100 ° C. for 3 hours. After addition of 6 mL of 1N KOH in methanol, the mixture was stirred at rt for 12 h and concentrated. The residue was dissolved in 50 mL of water, extracted with dichloromethane, the combined organic layers were dried over MgSO ₄ and the volatiles were removed. The residue was purified by column chromatography eluting on silica with a gradient of 10: 1 to 5: 1 dichloromethane: ethylacetate. 0.8 g (50%) of the title compound was isolated as a brownish solid.
[198] Triazolopyridine methylester derivatives were synthesized according to Example 3. The results were listed below, including Examples 4-19.
[199]
[200]
[201]
[202]
[203]
[204] Example numberdesignation 45-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 55-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 65-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 75-amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 85-Amino-2- (2-hydroxy-phenyl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 95-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 105-amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 115-amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 125-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 135-amino-2- (1-methyl-1H-pyrrol-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 145-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 155-amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 165-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 175-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 185-amino-2- (1H-pyrrol-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester 195-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl ester
[205] Example 20
[206] 5-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide
[207] To a solution of 35 mg (0.44 mmol) of diethylamine in 0.5 mL of dioxane was added 0.5 mL of methylaluminoxane (10% solution in toluene) (a variety of trimethylaluminum proved to give corresponding results instead of methylaluminoxane. Used) and stirred at room temperature for 1 hour. 31 mg (0.11 mmol) of 5-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7 in 1 ml dioxane Carboxylic acid methyl ester was added and the mixture was heated to 80 ° C. for 72 h. After addition of 0.4 ml of 1N HCl, the mixture is evaporated to dryness, the residue is dissolved in 1.5 ml of DMSO, filtered and the title compound separated by reverse phase HPLC eluting with a gradient of water / acetonitrile. Yielded 8.6 mg (25%).
[208] 1-H-NMR (500 MHz, DMSO): δ = 7.24 (s, 2H, NH ₂ ), 7.03 (d, J = 3 Hz, 1H, furanyl (3-H)), 6.79 (s, 1H, 8- H), 6.32 (d, J = 3 Hz, 1H, furanyl (4-H)), 6.09 (s, 1H, 6-H), 2.39 (s, 3H, CH ₃ ), 1.15 (m, 3H, NCH ₂ C H ₃ ), 1.08 (m, 3H, NCH ₂ C H ₃ ), signal for NCH ₂ under DMSO signal.
[209] MS m / e (%): 313 (M ⁺ , 100).
[210] Triazolopyridine carboxamide derivatives were synthesized according to Example 20. The results were listed below, including Examples 21-233.
[211]
[212]
[213]
[214]
[215]
[216]
[217]
[218]
[219]
[220]
[221]
[222]
[223]
[224]
[225]
[226]
[227]
[228]
[229]
[230]
[231]
[232]
[233]
[234]
[235]
[236]
[237]
[238]
[239]
[240] Example numberdesignation 215-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 22[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl -Metanon 23[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl -Metanon 245-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide 25(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone 265-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 27[5-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl- Metanon 28[5-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl- Metanon 295-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-ethyl-amide 30(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3,4-dihydro-1H-isoquinoline-2 -Work) -Methanone 315-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide 325-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-methyl-amide 335-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide 34(5-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone
[241] Example numberdesignation 355-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 365-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-butyl-amide 375-amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 385-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 395-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 405-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid [2- (2-fluoro-phenyl) -ethyl] -amide 415-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide 425-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-methoxy-benzylamide 435-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-fluoro-benzylamide 445-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (1-phenyl-ethyl) -amide 455-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid [2- (2-methoxy-phenyl) -ethyl] -amide 465-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide
[242] Example numberdesignation 475-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid hexylamide 485-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 495-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 505-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid [2- (2-chloro-phenyl) -ethyl] -amide 515-amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dibenzylamide 525-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 535-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl- (2-dimethylamino-ethyl )-amides 545-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid [2- (2-methoxy- Phenyl) -ethyl] -amide 555-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 565-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 575-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid [2- (2-fluoro- Phenyl) -ethyl] -amide 585-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide
[243] Example numberdesignation 595-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-ethyl-amide 605-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (1-phenyl-ethyl) -amide 615-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (pyridin-2-ylmethyl)- amides 625-amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide 635-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid hexylamide 645-amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 655-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide 66[5-amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidine-1- Sun-Methanone 675-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 685-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 69[5-amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidine-1- Sun-Methanone 705-amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclobutylamide
[244] Example numberdesignation 715-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid propylamide 725-amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylamide 735-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-butyl-amide 745-amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cycloheptylamide 755-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-phenethyl-amide 765-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-fluoro-benzyl )-amides 775-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-phenethyl-amide 785-Amino-2- (5-methoxy-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid [2- (2-chloro-phenyl ) -Ethyl] -amide 795-amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 805-amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 815-amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclobutylamide 825-amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid propylamide
[245] Example numberdesignation 835-Amino-2- (1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 845-Amino-2- (1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-butyl-amide 855-Amino-2- (1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-fluoro-benzyl) -amide 865-Amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 875-Amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide 885-Amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-ethyl-amide 895-Amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-butyl-amide 905-Amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-phenethyl-amide 915-Amino-2-pyridin-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-fluoro-benzyl) -amide 925-Amino-2- (1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 935-Amino-2- (1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide 945-Amino-2- (1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-ethyl-amide
[246] Example numberdesignation 955-amino-2- (1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclobutylamide 965-Amino-2- (1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-phenethyl-amide 975-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 3,4,5-trimethoxy-benzylamide 985-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 99(5-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone 1005-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide 1015-Amino-2- (2-hydroxy-phenyl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 102[5-amino-2- (2-hydroxy-phenyl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl-methanone 103(5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone 1045-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1055-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 106(5-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone
[247] Example numberdesignation 107(5-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone 108(5-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -morpholin-4-yl-methanone 1095-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 1105-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 1115-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 3,4,5-trimethoxy-benzylamide 1125-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 3,4,5-trimethoxy-benzyl amides 1135-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide 114[5-amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl ] -Methanone 115[5-amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -morpholin-4-yl- Metanon 1165-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-methyl-amide 1175-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 118[5-amino-2- (2-hydroxy-phenyl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl-methanone
[248] Example numberdesignation 1195-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1205-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 1215-Amino-2- (2-hydroxy-phenyl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 1225-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisopropylamide 1235-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 1245-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide 1255-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid indan-1-ylamide 1265-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (1-phenyl-ethyl) -amide 1275-amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 128(5-Amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone 129(5-Amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone 1305-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide
[249] Example numberdesignation 1315-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 132[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -morpholin-4-yl- Metanon 1335-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 3,4,5-trimethoxy- Benzylamide 134[5-amino-2- (1-methyl-1H-pyrrol-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidine-1- Sun-Methanone 1355-Amino-2- (1-methyl-1 H-pyrrol-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 1365-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 1375-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1385-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 139[5-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -morpholin-4-yl-meta Paddy field 1405-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-methyl-amide 1415-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 1425-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 3,4-dimethoxy-benzylamide
[250] Example numberdesignation 1435-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide 1445-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 1455-amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1465-amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 1475-amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 1485-Amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide 1495-amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid indan-1-ylamide 150(5-Amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone 151(5-Amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone 1525-Amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-methyl-amide 1535-amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 1545-amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide
[251] Example numberdesignation 155(5-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone 1565-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 1575-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 1585-Amino-2- (2-hydroxy-phenyl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1595-Amino-2- (2-hydroxy-phenyl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 1605-Amino-2- (2-hydroxy-phenyl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 1615-amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1625-amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 1635-Amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 1645-Amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 1655-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 1665-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide
[252] Example numberdesignation 1675-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 1685-Amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1695-amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 170[5-amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl -Metanon 171[5-amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl -Metanon 1725-amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide 1735-Amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 1745-Amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 1755-Amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 1765-Amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-methoxy-benzylamide 1775-Amino-2- (4-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 3,4,5-trimethoxy- Benzylamide 1785-amino-2- (1-methyl-1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide
[253] Example numberdesignation 1795-amino-2- (1-methyl-1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 1805-amino-2- (1-methyl-1H-pyrrole-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide 1815-Amino-2- (1-methyl-1 H-pyrrol-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 1825-Amino-2- (1-methyl-1 H-pyrrol-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 1835-Amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-methoxy-benzylamide 1845-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1855-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 1865-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisopropylamide 1875-amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid indan-1-ylamide 188[5-amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl -Metanon 189[5-amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl -Metanon 1905-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (1-phenyl-ethyl) -amide
[254] Example numberdesignation 1915-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 1925-Amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide 1935-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide 1945-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide 1955-amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 196[5-amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl -Metanon 1975-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide 1985-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (1-phenyl-ethyl) -amide 1995-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 2005-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 2015-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide 2025-Amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 3,4,5-trimethoxy- Benzylamide
[255] Example numberdesignation 2035-amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid indan-1-ylamide 2045-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-methyl-amide 2055-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-chloro-benzylamide 2065-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-fluoro-benzylamide 2075-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-methoxy-benzylamide 2085-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 3,4-dimethoxy-benzylamide 2095-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid indan-1-ylamide 2105-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide 2115-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (1-phenyl-ethyl) -amide 2125-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-chloro-benzylamide 2135-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-fluoro-benzylamide 2145-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide
[256] Example numberdesignation 2155-Amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-methoxy-benzylamide 2165-amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide 2175-Amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (1-phenyl-ethyl) -amide 2185-Amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 2195-Amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 2205-Amino-2-phenyl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide 2215-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide 2225-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide 2235-amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid indan-1-ylamide 2245-amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide 2255-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (1-phenyl-ethyl) -amide 2265-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-methyl-amide
[257] Example numberdesignation 2275-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-fluoro-benzylamide 2285-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide 2295-Amino-2-thiophen-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-methoxy-benzylamide 2305-Amino-2-furan-3-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-chloro-benzylamide 2315-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-methoxy-benzylamide 2325-amino-2- (3-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 2335-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide 2345-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexylamide 235[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl- Metanon 236[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl- Metanon 237[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -morpholin-4-yl-meta Paddy field 2385-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzylamide
[258] Example numberdesignation 2395-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 2405-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-chloro-benzylamide 2415-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-bromo-benzylamide 2425-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide 2435-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide 2445-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-chloro-benzylamide 2455-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 4-fluoro-benzylamide 2465-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid 2-methoxy-benzylamide 2475-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylmethyl-methyl-amide 2485-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dimethylamide 249[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -azetidin-1-yl-meta Paddy field 2505-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-methyl-amide
[259] Example numberdesignation 2515-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-methyl-amide 2525-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide 253[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,6-dihydro- 2H-pyridin-1-yl) -methanone 254[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-pyrrolidine -1-yl) -methanone 2555-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide 256[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -thiomorpholin-4-yl- Metanon 257[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,6-dimethyl-mor Polin-4-yl) -Methanone 258[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dimethyl-pi Rollidin-1-yl) -Methanone 2591- [5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -piperidine-4 Carboxylic acid amides 2605-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid bis- (2-methoxy-ethyl)- amides 2615-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-ethyl-amide 2625-Amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-pyridin-4-ylmethyl-amide
[260] Example numberdesignation 263[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-phenyl-3,6 -Dihydro-2H-pyridin-1-yl) -methanone 2645-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-methyl-amide 265[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dihydro -Pyrrole-1-yl) -methanone 2665-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-prop-2-ynyl-amide 2675-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-methyl-amide 2685-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide 2695-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid isopropyl-methyl-amide 270[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-pyrroli Din-1-yl) -methanone 2715-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-methyl-amide 2725-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide 273[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dimethyl- 2,5-dihydro-pyrrole-1-yl) -methanone 2745-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diallylamide
[261] Example numberdesignation 275[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dimethyl- Pyrrolidin-1-yl) -Methanone 2765-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisopropylamide 2775-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-ethyl-amide 2785-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-pentyl-amide 2795-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (2-dimethylamino-ethyl) -methyl -amides 2805-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-methyl-amide 281(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,5-dihydro-pyrrol-1-yl ) -Methanone 2825-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-prop-2-ynyl-amide 2835-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-methyl-amide 2845-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide 2855-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid isopropyl-methyl-amide 286(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-pyrrolidin-1-yl) -Metanon
[262] Example numberdesignation 2875-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-methyl-amide 2885-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide 289(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -thiazolidin-3-yl-methanone 2905-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diallylamide 2915-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-ethyl-amide 2925-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-pentyl-amide 2935-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dimethylamide 294[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,6-dihydro -2H-pyridin-1-yl) -methanone 295[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3-methyl-piperi Din-1-yl) -methanone 296[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -azepan-1-yl- Metanon 297[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -thiomorpholin-4-yl -Metanon 2985-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylmethyl-propyl-amide
[263] Example numberdesignation 299[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-ethyl-piperazine -1-yl) -methanone 3001- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -piperidine- 4-carboxylic acid amide 301(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,5-dimethyl-pyrrolidine-1- Sun) -Methanone 302(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,5-dimethyl-2,5-dihydro -Pyrrole-1-yl) -methanone 303[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,6-dimethyl- Piperidin-1-yl) -methanone 304[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,6-dimethyl- Morpholin-4-yl) -methanone 3055-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid bis- (2-methoxy-ethyl) -amides 3065-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-phenethyl-amide 3075-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-ethyl-amide 3085-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl- (2-pyridin-2-yl -Ethyl) -amide 3095-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (2-diethylamino-ethyl)- Ethyl-amide 310[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-benzyl-piperazine -1-yl) -methanone
[264] Example numberdesignation 3115-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid bis- (2,2,2-tri Fluoro-ethyl) -amide 312[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-phenyl-3, 6-dihydro-2H-pyridin-1-yl) -methanone 3135-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dibenzylamide 3145-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-pyridin-4-ylmethyl-amide 315(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3,6-dihydro-2H-pyridine-1 -Work) -Methanone 316(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3-methyl-piperidin-1-yl) -Metanon 317(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azpan-1-yl-methanone 318(5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -thiomorpholin-4-yl-methanone 3195-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylmethyl-propyl-amide 320(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,6-dimethyl-piperidine-1- Sun) -Methanone 3215-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid bis- (2-methoxy-ethyl) -amide 3225-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-phenethyl-amide
[265] Example numberdesignation 3235-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-ethyl-amide 3245-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl- (2-pyridin-2-yl-ethyl) -amide 3255-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-pyridin-4-ylmethyl-amide 326(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(4-phenyl-3,6-dihydro-2H -Pyridin-1-yl) -methanone 3275-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dibenzylamide 3285-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethylamide 329(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl) -Metanon 330(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(4-methyl-piperidin-1-yl) -Metanon 3315-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dipropylamide 332(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azokane-1-yl-methanone 333(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3,5-dimethyl-piperidine-1- Sun) -Methanone 3345-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-propyl-amide
[266] Example numberdesignation 3355-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethylamide 336[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-piperi Din-1-yl) -methanone 337[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-methyl-piperi Din-1-yl) -methanone 3385-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dipropylamide 339[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -azokan-1-yl- Metanon 3405-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide 341[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,5-dimethyl- Piperidin-1-yl) -methanone 3425-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-propyl-amide 3435-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-methyl-amide 3445-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-cyclopentyl-amide 3455-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide 3465-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisobutylamide
[267] Example numberdesignation 347[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,4-dihydro -1H-isoquinolin-2-yl) -methanone 3485-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-cyclohexyl-amide 349[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(octahydro-quinoline-1 -Work) -Methanone 350[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(octahydro-isoquinoline- 1-day) -methanone 3515-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-isopropyl-amide 3525-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-pyridin-2-yl -Ethyl) -amide 353[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-phenyl-piperazine -1-yl) -methanone 354[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,4,5, 6-tetrahydro-2H- [2,3 '] bipyridinyl-1-yl) -methanone 355[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(1,3,4, 9-tetrahydro-b-carboline-2-yl) -methanone 3561- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -piperidine- 3-carboxylic acid diethylamide 357(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,6-dimethyl-piperidine-1- Sun) -Methanone 358(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(cis-2,6-dimethyl-piperidine- 1-day) -methanone 359[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-[(2R, 5R)- Trans-2,5-dimethyl-pyrrolidin-1-yl] -methanone 360[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(cis-2,6- Dimethyl-morpholin-4-yl) -methanone
[268] Example 361
[269] 2,6-diamino-isonicotinamide
[270] A solution of 3.9 g (20 mmol) of 2,6-diamino-isonicotinic acid methyl ester in 200 ml of methanol was treated with gaseous ammonia at 0 ° C. for 1 hour. The mixture was heated to 62 ° C. for 36 h in an autoclave (4 bar), then filtered through decalite and evaporated to dryness. 3.5 g (quant) of the title compound were obtained as a yellow solid.
[271] The analytical sample was further purified via column chromatography eluting with 30: 10: 1 DCM / MeOH / NH ₃ aqueous solution on silica to give pure material.
[272]
[273] Example 362
[274] 4-aminomethyl-pyridine-2,6-diamine
[275] 0.455 mL (4.8 mmol) of borane-dimethylsulfide-complex was added dropwise to the refluxing suspension of 0.5 g (3.29 mmol) of 2,6-diamino-isonicotinamide in 3 mL of THF and the mixture was refluxed for 4 days. . After cooling to room temperature, 0.548 mL of 6N HCl was added and the mixture was neutralized with 2N NaOH. The mixture was concentrated under reduced pressure and the residue was purified by column chromatography eluting with 100: 100: 1 aqueous DCM / MeOH / NH ₃ solution on silica to give 166 mg (36%) of the title compound as a yellow solid. .
[276]
[277] Example 363
[278] 2-Bromo-N- (2,6-diamino-pyridin-4-ylmethyl) -benzamide
[279] A solution of 172.5 mg (1.25 mmol) of 4-aminomethyl-pyridine-2,6-diamine in 5 ml pyridine was treated with 275 mg (1.25 mmol) of o -bromobenzoylchloride and a catalytic amount of 4-dimethylaminopyridine And stirred at room temperature for 2.5 hours. The mixture was evaporated to dryness and the residue was purified by column chromatography eluting with 9: 1 dichloromethane / methanol on silica to give 81 mg (20%) of the title compound.
[280]
[281] Example 364
[282] Cyclopentanecarboxylic acid (2,6-diamino-pyridin-4-ylmethyl) -amide
[283] A solution of 205.6 mg (1.49 mmol) of 4-aminomethyl-pyridine-2,6-diamine in 5 mL of pyridine was treated with 198 mg (1.49 mmol) of cyclopentane carboxylic acid chloride and a catalytic amount of 4-dimethylaminopyridine, Stir at room temperature for 2.5 hours. The mixture was evaporated to dryness and the residue was purified by column chromatography eluting with 9: 1 dichloromethane / methanol on silica to give 93 mg (26%) of the title compound.
[284]
[285] Example 365
[286] Cyclopentanecarboxylic acid [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-ylmethyl] -amide
[287] 40.2 mg (0.187 mmol, 1.1 equiv) of o -methyl in a solution of 39 mg (0.17 mmol) of cyclopentanecarboxylic acid (2,6-diamino-pyridin-4-ylmethyl) -amide in 1.4 mL dioxane Rensulfonylhydroxylamine and 38.6 mg (0.221 mmol, 1.3 equiv) of 5-bromo-2-furaldehyde were added after 2 hours. The mixture was heated at 100 ° C. for 2.5 h and then 0.17 mL 1N KOH in MeOH was added. The reaction vessel was opened and the mixture was stirred at rt for 16 h, evaporated and dried. The residue was dissolved in 4.5 ml of water and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over MgSO ₄ and evaporated. The residue was purified by column chromatography eluting on silica to give 12 mg (21%) of the title compound.
[288]
[289] Example 366
[290] Cyclopentanecarboxylic acid [5-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-ylmethyl] -amide
[291] The title compound is cyclopentanecarboxylic acid (2,6-diamino-pyridin-4-ylmethyl) -amide, o -mesitylene-sulfonylhydroxylamine and 5-methyl-2-furaldehyde from the general method of Example 365. It was prepared according to. Purification was carried out using column chromatography eluting with 1: 2 dichloromethane / ethyl acetate on silica.
[292]
[293] Example 367
[294] N- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-ylmethyl] -2-bromo -Benzamide
[295] The title compound is derived from 2-bromo-N- (2,6-diamino-pyridin-4-ylmethyl) -benzamide, o -mesitylene-sulfonylhydroxylamine and 5-bromo-2-furaldehyde It was prepared according to the general method of Example 365. Purification was carried out using column chromatography eluting with 1: 2 dichloromethane / ethyl acetate on silica.
[296]
[297] Example 368
[298] N- [5-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-ylmethyl] -2-bromo- Benzamide
[299] The title compound is carried out from 2-bromo-N- (2,6-diamino-pyridin-4-ylmethyl) -benzamide, o -mesitylene-sulfonylhydroxylamine and 5-methyl-2-furaldehyde Example 365 was prepared according to the general method. Purification was carried out using column chromatography eluting with 1: 2 dichloromethane / ethyl acetate on silica.
[300]
[301] Example 369
[302] 2,6-bis-acetylamino-isonicotinic acid methyl ester
[303] A mixture of 3 g (17.95 mmol) of 2,6-diamino-isonicotinic acid methyl ester, 10 mL of pyridine and 7.46 mL (78.9 mmol) of acetic anhydride is stirred at room temperature for 1 hour and then at 80 ° C. for 1 hour. It was. The volatiles were removed under reduced pressure and the residue was dissolved in ethyl acetate and Na ₂ CO ₃ solution. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over MgSO ₄ and concentrated to give 3.79 g (84%) of the title compound as white crystals.
[304]
[305] Example 370
[306] 2,6-bis-acetylamino-N-methoxy-N-methyl-isonicotinamide
[307] A mixture of 5.33 g (54.7 mmol) of N, O-dimethylhydroxylamine in 40 mL of DCM was treated with a 2M trimethylaluminum solution in toluene at 0 ° C. and stirred at 0 ° C. for an additional hour. 4.48 g (18.23 mmol) of 2,6-bis-acetylamino-N-methoxy-N-methyl-isonicotinamide and then 8.65 mL of pyridine were added slowly. The mixture was stirred at rt for 16 h. 10 ml of 37% HCl was added and the mixture was poured into 300 ml of MeOH. Decalite was added, the mixture was filtered, the filtrate was evaporated and dried. The residue was further purified by column chromatography eluting with DCM: MeOH on silica to afford 3.48 g (49%) of the title compound.
[308] MS m / z (%): 281.2 (M + H ⁺ , 100).
[309] Example 371
[310] (2,6-Diamino-pyridin-4-yl)-(4-fluoro-phenyl) -methanone
[311] A solution of 1M 4-fluorophenylmagnesium bromide in THF at room temperature in a solution of 0.5 g (1.78 mmol) of 2,6-bis-acetylamino-N-methoxy-N-methyl-isonicotinamide in 8 ml THF at room temperature 7.14 mL (7.14 mmol) was added and stirred at room temperature for 80 minutes, then at 40 ° C. for 2 hours. After cooling to room temperature, 0.8 ml of 37% HCl was added and the mixture was evaporated and dried. The residue was dissolved in ethyl acetate and 2M Na ₂ CO ₃ . The aqueous layer was extracted with ethyl acetate and the combined organic fractions were dried over MgSO ₄ and evaporated to dryness. The residue was dissolved in 3 ml of MeOH and 1 ml of 37% HCl and heated at reflux for 4 hours. After evaporation to dryness, the residue was dissolved in ethyl acetate and 2M Na ₂ CO ₃ . The aqueous layer was extracted with ethyl acetate and the combined organic fractions were dried over MgSO ₄ and evaporated to dryness. The title compound was further purified by reverse phase HPLC eluting with acetonitrile / water gradient to yield 131 mg (32%) of yellow crystals.
[312]
[313] Example 372
[314] (2,6-Diamino-pyridin-4-yl) -phenyl-methanone
[315] The title compound was prepared according to the general method of Example 371 from 2,6-bis-acetylamino-N-methoxy-N-methyl-isonicotinamide and phenylmagnesium bromide. Purification was performed using reverse phase HPLC eluting with acetonitrile / water gradient. Yield: 37%
[316]
[317] Example 373
[318] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-fluoro-phenyl ) -Methanone
[319] To a solution of 43 mg (0.177 mmol) of (2,6-diamino-pyridin-4-yl)-(4-fluoro-phenyl) -methanone in 0.5 ml dioxane 38.7 mg (0.194 mmol, 1.1 Equivalent) of o -mesitylenesulfonylhydroxylamine and 40 mg (0.23 mmol, 1.3 equivalents) of 5-bromo-2-furaldehyde after 1 hour were added and stirred at 80 ° C for 30 minutes. After addition of 1N KOH, the mixture was stirred at rt for 12 h. The mixture was purified by preparative reverse phase HPLC eluting with a gradient of acetonitrile / water to afford 4.5 mg (11%) of the title compound.
[320] Example 374
[321] (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(4-fluoro-phenyl) -methanone
[322] The title compound (MS m / e (%): 340 (M + H ⁺ , 100)) was found (2,6-diamino-pyridin-4-yl)-(4-fluoro-phenyl) -methanone, o From -mesitylene-sulfonylhydroxylamine and thiazole-2-carbaldehyde, according to the general method of example 373. Purification was performed using reverse phase HPLC eluting with acetonitrile / water gradient.
[323] Example 375
[324] (5-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(4-fluoro-phenyl) -methanone
[325] The title compound (MS m / e (%): 334 (M + H ⁺ , 100)) is (2,6-diamino-pyridin-4-yl)-(4-fluoro-phenyl) -methanone, o From -mesitylene-sulfonylhydroxylamine and pyridine-2-carbaldehyde, according to the general method of example 373. Purification was performed using reverse phase HPLC eluting with acetonitrile / water gradient.
[326] Example 376
[327] [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -phenyl-methanone
[328] The title compound (MS m / e (%): 383 (M + H ⁺ , 100)) was obtained from (2,6-diamino-pyridin-4-yl) -phenyl-methanone, o -mesitylene-sulfonylhydride. Prepared according to the general method of Example 373 from loxylamine and 5-bromo-2-furaldehyde. Purification was performed using reverse phase HPLC eluting with acetonitrile / water gradient.
[329] Example 377
[330] (5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -phenyl-methanone
[331] The title compound (MS m / e (%): 322 (M + H ⁺ , 100)) was found (2,6-diamino-pyridin-4-yl) -phenyl-methanone, o -mesitylene-sulfonylhydride. Prepared according to the general method of example 373 from the loxylamine and thiazole-2-carbaldehyde. Purification was performed using reverse phase HPLC eluting with acetonitrile / water gradient.
[332] Example 378
[333] (5-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -phenyl-methanone
[334] The title compound (MS m / e (%): 316 (M + H ⁺ , 100)) was found (2,6-diamino-pyridin-4-yl) -phenyl-methanone, o -mesitylene-sulfonylhydride. Prepared according to the general method of example 373 from the loxylamine and pyridine-2-carbaldehyde. Purification was performed using reverse phase HPLC eluting with acetonitrile / water gradient.
[335] According to Example 20, the following triazolopyridine carboxamide derivatives were synthesized. The results were listed below, including Examples 379-435.
[336]
[337]
[338]
[339]
[340]
[341] Example numberdesignation 379(5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(octahydro-quinolin-1-yl) -methanone 380(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(octahydro-isoquinolin-2-yl) -meta Paddy field 3811- (5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carbonyl) -piperidine-3-carboxylic acid diethylamide 3825-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-cyclopentyl-amide 3835-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide 3845-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dimethylcarbamoylmethyl-methyl-amide 385[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(S-2-methoxy Methyl-pyrrolidin-1-yl) -methanone 386[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(R-2-methoxy Methyl-pyrrolidin-1-yl) -methanone 387[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(S, S-2, 5-bis-methoxymethyl-pyrrolidin-1-yl) -methanone 3881- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -L-pyrroli Dean-2-carboxylic acid amide 3891- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -D-pyrroli Dean-2-carboxylic acid amide 3901- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -pyrrolidine- 2-carboxylic acid dimethylamide 391N- {1- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -pi Rollidin-3-yl} -acetamide 392N- {1- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -pi Ralidin-3-yl} -N-methyl-acetamide
[342] Example numberdesignation 393[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(5-ethyl-2- Methyl-piperidin-1-yl) -methanone 3941- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -piperidine- 3-carboxylic acid amide 3955-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (2-methoxy-ethyl) -methyl -amides 3965-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-methoxy-ethyl) -amides 3975-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (2-methoxy-ethyl) -methyl-amide 3985-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-methoxy-ethyl) -amide 3995-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dimethylcarbamoylmethyl-methyl-amide 400(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(S-2-methoxymethyl-pyrrolidine- 1-day) -methanone 401(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(R-2-methoxymethyl-pyrrolidine- 1-day) -methanone 4021- (5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carbonyl) -pyrrolidine-2-carboxylic acid dimethylamide 403N- [1- (5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-carbonyl) -pyrrolidin-3-yl ] -N-methyl-acetamide 404(5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(5-ethyl-2-methyl-piperidine- 1-day) -methanone 4055-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisobutylamide 4065-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-methyl-amide
[343] Example numberdesignation 4075-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-prop-2-ynyl-amide 408(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,5-dihydro-pyrrol-1-yl) -Metanon 4095-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-methyl-amide 410(5-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone 4115-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid isopropyl-methyl-amide 4125-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide 413(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-pyrrolidin-1-yl)- Metanon 4145-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide 415(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,5-dimethyl-2,5-dihydro- Pyrrole-1-yl) -methanone 4165-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diallylamide 417(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azpan-1-yl-methanone 418(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl)- Metanon 419(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl)- Metanon 4205-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dipropylamide
[344] Example numberdesignation 4215-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-ethyl-amide 422(5-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azokane-1-yl-methanone 423(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3,5-dimethyl-piperidin-1-yl ) -Methanone 4245-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylmethyl-propyl-amide 425(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(R-2-methoxymethyl-pyrrolidine-1 -Work) -Methanone 426(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(S-2-methoxymethyl-pyrrolidine-1 -Work) -Methanone 4275-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-propyl-amide 4285-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dimethylcarbamoylmethyl-methyl-amide 4295-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-cyclopentyl-amide 430(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(5-ethyl-2-methyl-piperidine-1 -Work) -Methanone 4315-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-pyridin-4-ylmethyl-amide 4321- (5-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carbonyl) -pyrrolidine-2-carboxylic acid dimethylamide 4335-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide 4341- (5-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carbonyl) -piperidine-3-carboxylic acid diethylamide 4355-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dibenzylamide

权利要求:
Claims (24)
[1" claim-type="Currently amended] A compound of formula (I) or a pharmaceutically acceptable salt thereof:
Formula I

Where
R ¹ is lower alkoxy, cycloalkyl or aryl unsubstituted or substituted with halogen or lower alkoxy, or —NR′R ″ (wherein R ′ and R ″ independently of one another is hydrogen or in the crowd consisting of halogen or lower alkoxy) Lower alkyl, lower alkenyl, lower alkynyl or-(CR ₂ ) _n -aryl unsubstituted or substituted with one to three substituents selected, or-(CH ₂ ) _{n + 1} NR ₂ ,-(CH ₂ ) _n -Pyridinyl,-(CH ₂ ) _n -indanyl,-(CH ₂ ) _n -cycloalkyl,-(CH ₂ ) _n -O-lower alkyl,-(CH ₂ ) _n -C (O) -NR ₂ ,-(CH ₂ ) _n -CF _3, or R 'and R "together with the N atom attached thereto are pyrrolidin-1-yl, piperidin-1-yl, 3,4-dihydro-1H Isoquinolin-2-yl, morpholinyl, azatidin-1-yl, 3,6-dihydro-2H-pyridin-1-yl, thiomorpholinyl, 2,5-dihydro-pyrrole-1- Yl, thiazolidin-3-yl, piperazinyl, azocan-1-yl, azepan-1-yl, octahydroquinolin-1-yl, octahydr Forms quinolin-2-yl, 1,3,4,9-tetrahydro-b-carboline-2-yl, the ring being lower alkyl, phenyl, benzyl, pyridyl, -C (O) -NR ₂ ,-(CH ₂ ) _n -O-lower alkyl or -NR-C (O) -lower alkyl, which may be substituted or unsubstituted with 1 to 3 substituents selected from the group consisting of;
R ² is aryl or a 5 or 6 membered heteroaryl group, said ring being unsubstituted or substituted with lower alkyl, halogen, hydroxy or lower alkoxy;
X is a bond or -N (R) CH _2- ;
R is hydrogen or lower alkyl;
n is 0, 1, 2, 3, 4, 5 or 6.
[2" claim-type="Currently amended] A compound of formula (I) or a pharmaceutically acceptable salt thereof:
Formula I

Where
R ¹ is lower alkoxy, cycloalkyl or aryl unsubstituted or substituted with halogen or lower alkoxy, or —NR′R ″ (wherein R ′ and R ″ independently of one another is hydrogen or in the crowd consisting of halogen or lower alkoxy) Lower alkyl, lower alkenyl, lower alkynyl or-(CR ₂ ) _n -aryl unsubstituted or substituted with one to three substituents selected, or-(CH ₂ ) _{n + 1} NR ₂ ,-(CH ₂ ) _n -Pyridinyl,-(CH ₂ ) _n -indanyl,-(CH ₂ ) _n -cycloalkyl,-(CH ₂ ) _n -O-lower alkyl,-(CH ₂ ) _n -CF _3, or R 'and R ″ together with the N atoms attached to them pyrrolidin-1-yl, piperidin-1-yl, 3,4-dihydro-1H-isoquinolin-2-yl, morpholinyl, azatidine- 1-yl, 3,6-dihydro-2H-pyridin-1-yl, thiomorpholinyl, 2,5-dihydro-pyrrole-1-yl, thiazolidin-3-yl, piperazinyl, azo Can-1-yl, octahydroquinolin-1-yl, octahydroquinolin-2-yl, 1,3,4,9-tetraha Draw -b- car Boleyn-2 to form a one, the ring is lower alkyl, phenyl, benzyl or pyridyl substituted by one to three substituents selected from the group consisting of which may be unsubstituted or shown below);
R ² is aryl or a 5 or 6 membered heteroaryl group, said ring being unsubstituted or substituted with lower alkyl, halogen, hydroxy or lower alkoxy;
X is a bond or -N (R) CH _2- ;
R is hydrogen or lower alkyl;
n is 0, 1, 2, 3, 4, 5 or 6.
[3" claim-type="Currently amended] The method according to claim 1 or 2,
A compound of formula I, wherein X is a bond.
[4" claim-type="Currently amended] The method of claim 3, wherein
R ¹ is —NR′R ″ wherein R ′ and R ″ are independently of each other lower alkyl, lower alkenyl, lower alkynyl, — (CH ₂ ) _n —C (O) —N (CH ₃ ) ₂ , -(CH ₂ ) _n -OCH ₃ ,-(CH ₂ ) _n -cycloalkyl or-(CH ₂ ) _n -pyridin-2-yl), and R ² is furyl unsubstituted or substituted with halogen or lower alkyl; A compound of formula I, which is thiophenyl.
[5" claim-type="Currently amended] The method of claim 4, wherein
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide,
5-amino-2- (5-methyl-thiophen-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide,
5-amino-2- (5-methyl-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide,
5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide,
(5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl metanon,
5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide,
5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-methyl-amide,
5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-prop-2-ynyl-amide ,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-methyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid isopropyl-methyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-methyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-isopropyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diallylamide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisopropylamide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-ethyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-pentyl-amide,
5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (2-dimethylamino-ethyl) -methyl -amides,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylmethyl-propyl-amide,
5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl- (2-pyridin-2-yl -Ethyl) -amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dipropylamide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-methyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-cyclopentyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclohexyl-ethyl-amide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisobutylamide,
5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-pyridin-2-yl -Ethyl) -amide,
1- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -piperidine- 3-carboxylic acid diethylamide,
5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dimethylcarbamoylmethyl-methyl-amide,
5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid (2-methoxy-ethyl) -methyl -Amide or
5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl- (2-methoxy-ethyl) A compound of formula I, which is an amide.
[6" claim-type="Currently amended] The method of claim 3, wherein
R ¹ is —NR′R ″ wherein R ′ and R ″ are independently of each other lower alkyl, lower alkenyl, lower alkynyl,-(CH ₂ ) _n -phenyl or-(CH ₂ ) _n -pyridinyl ) And R ² is thiazolyl.
[7" claim-type="Currently amended] The method of claim 6,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butylamide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diethylamide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-methyl-amide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-prop-2-ynyl-amide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-methyl-amide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid methyl-propyl-amide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid isopropyl-methyl-amide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid butyl-methyl-amide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-pyridin-4-ylmethyl-amide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dibenzylamide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethylamide,
5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dipropylamide or
5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diisobutylamide.
[8" claim-type="Currently amended] The method of claim 3, wherein
R ¹ is —NR′R ″ wherein R ′ and R ″ together with the N atom attached to them are pyrrolidinyl, piperidinyl, morpholinyl, 3,6-dihydro-2H-pyridine-1- 1,2,5-dihydro-pyrrole-1-yl, azocan-1-yl, the ring being lower alkyl, lower alkoxy, -C (O) -NH ₂ , -C (O) N ( CH ₃ ) ₂ , -N (CH ₃ ) -C (O) -CH ₃ , which may be unsubstituted or substituted, and R ² is halogen substituted or unsubstituted furyl.
[9" claim-type="Currently amended] The method of claim 8,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -pyrrolidin-1-yl -Methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -piperidin-1-yl -Methanone,
(5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone,
(5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone,
(5-amino-2-furan-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -morpholin-4-yl-methanone,
[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,6-dihydro- 2H-pyridin-1-yl) -methanone,
[5-amino-2- (5-chloro-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-pyrrolidine -1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dihydro -Pyrrole-1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-pyrroli Din-1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dimethyl- 2,5-dihydro-pyrrol-1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,5-dimethyl- Pyrrolidin-1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2,6-dimethyl- Morpholin-4-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(2-methyl-piperi Din-1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(4-methyl-piperi Din-1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl] -azokan-1-yl- Methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(3,5-dimethyl- Piperidin-1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-[(2R, 5R)- Trans-2,5-dimethyl-pyrrolidin-1-yl] -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(cis-2,6- Dimethyl-morpholin-4-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(S-2-methoxy Methyl-pyrrolidin-1-yl) -methanone,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(R-2-methoxy Methyl-pyrrolidin-1-yl) -methanone,
1- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -L-pyrroli Din-2-carboxylic acid amide,
1- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -D-pyrroli Din-2-carboxylic acid amide,
1- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -pyrrolidine- 2-carboxylic acid dimethylamide,
N- {1- [5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -pi Ralidin-3-yl} -N-methyl-acetamide,
[5-amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridin-7-yl]-(5-ethyl-2- Methyl-piperidin-1-yl) -methanone or
1- [5-Amino-2- (5-bromo-furan-2-yl)-[1,2,4] triazolo [1,5-a] pyridine-7-carbonyl] -piperidine- A compound of formula (I) which is 3-carboxylic acid amide.
[10" claim-type="Currently amended] The method of claim 3, wherein
R ¹ is —NR′R ″ wherein R ′ and R ″ together with the N atom attached to them are pyrrolidinyl, piperidinyl, octahydroquinolin-1-yl, 2,5-dihydro-pyrrole- 1-yl, thiazolidinyl, thiazolyl, azepan-1-yl or azocan-1-yl, the ring may be substituted or unsubstituted with lower alkyl, and R ² is thiazolyl Compounds of formula (I).
[11" claim-type="Currently amended] The method of claim 10,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -pyrrolidin-1-yl-methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -piperidin-1-yl-methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,5-dihydro-pyrrol-1-yl ) -Methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-pyrrolidin-1-yl) -Methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -thiazolidin-3-yl-methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azpan-1-yl-methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl) -Methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(4-methyl-piperidin-1-yl) -Methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azokane-1-yl-methanone,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3,5-dimethyl-piperidine-1- Sun,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2,6-dimethyl-piperidine-1- Sun,
(5-amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(cis-2,6-dimethyl-piperidine- 1-day) -methanone or
(5-Amino-2-thiazol-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(octahydro-quinolin-1-yl) -metatan Compound of formula (I).
[12" claim-type="Currently amended] The method of claim 3, wherein
R ¹ is -NR'R "where R 'and R" together with the N atom attached to them are pyrrolidin-1-yl, azepan-1-yl, piperidin-1-yl, azocan Forming -1-yl, wherein the ring may be unsubstituted or substituted with lower alkyl, lower alkoxy), and R ² is pyridyl.
[13" claim-type="Currently amended] The method of claim 12,
(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-pyrrolidin-1-yl)- Methanone,
(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azpan-1-yl-methanone,
(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl)- Methanone,
(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(2-methyl-piperidin-1-yl)- Methanone,
(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -azokane-1-yl-methanone,
(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl)-(3,5-dimethyl-piperidin-1-yl ) -Metanon or
(5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridin-7-yl) -R-2-methoxymethyl-pyrrolidine-1- (I) -Methanone.
[14" claim-type="Currently amended] The method of claim 3, wherein
R ¹ is —NR′R ″ wherein R ′ and R ″ are independently of each other lower alkenyl, lower alkyl, — (CH ₂ ) _n -cycloalkyl, — (CH ₂ ) _n -pyridinyl, or — (CH ₂ ) A compound of formula I wherein _n -phenyl and R ² is pyridyl.
[15" claim-type="Currently amended] The method of claim 14,
5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid diallylamide,
5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid cyclopropylmethyl-propyl-amide,
5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid allyl-cyclopentyl-amide,
5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid ethyl-pyridin-4-yl-methyl-amide,
5-amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid benzyl-isopropyl-amide or
5-Amino-2-pyridin-2-yl- [1,2,4] triazolo [1,5-a] pyridine-7-carboxylic acid dibenzylamide.
[16" claim-type="Currently amended] The method according to claim 1 or 2,
A compound of formula I, wherein X is -N (R) CH _2- .
[17" claim-type="Currently amended] The method of claim 16,
R ¹ is a substituted or unsubstituted cycloalkyl or aryl by halogen, R ² is substituted with halogen or methyl unsubstituted furyl or thiazolyl A compound of formula I.
[18" claim-type="Currently amended] 18. A medicament containing at least one compound of formula (I) according to any one of claims 1 to 17 and a pharmaceutically acceptable excipient.
[19" claim-type="Currently amended] The method of claim 18,
A medicament for treating a disease associated with adenosine receptors.
[20" claim-type="Currently amended] a) reacting a compound of formula I-1 with a compound of formula II to yield a compound of formula I-2, or b) reacting a compound of formula III with a compound of formula V in the presence of a compound of formula IV To obtain a compound of Formula 3, or c) reacting a compound of Formula VI with HCl, a compound of Formula IV and a compound of Formula V, in order to obtain a compound of Formula I-4, or d) replacing one or more substituents R ¹ or R ² A process for the preparation of a compound of formula (I) as defined in claim 1 comprising modifying within the definition given above and converting the obtained compound to a pharmaceutically acceptable acid addition salt, if necessary:
Formula I-1

Formula II
HNR'R "
Formula I-2

Formula III

Formula IV

Formula V
R ² CHO
Formula I-3

Formula VI

Formula I-4

Where
R ¹ , R ² , R 'and R "are as defined above.
[21" claim-type="Currently amended] The method according to any one of claims 1 to 17,
A compound prepared by the process according to claim 20 or an equivalent method.
[22" claim-type="Currently amended] Use of a compound according to any one of claims 1 to 17 for treating a disease.
[23" claim-type="Currently amended] Use of a compound according to any one of claims 1 to 17 in the manufacture of a corresponding medicament for the treatment of diseases associated with adenosine A _2A receptors.
[24" claim-type="Currently amended] Invention as defined above.

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BR0116193A|2003-09-23|

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CN1486314A|2004-03-31|

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JP2004521096A|2004-07-15|

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KR100540628B1|2006-01-11|

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DK1347974T3|2005-03-14|

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引用文献:

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公开号 | 申请日 | 公开日 | 申请人 | 专利标题

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法律状态:
2000-12-15|Priority to EP00127567.6

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2000-12-15|Priority to EP00127567

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2001-12-07|Application filed by 에프. 호프만-라 로슈 아게

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2001-12-07|Priority to PCT/EP2001/014399

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2003-07-18|Publication of KR20030061446A

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2006-01-11|Application granted

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2006-01-11|Publication of KR100540628B1

优先权:

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申请号 | 申请日 | 专利标题

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EP00127567.6|2000-12-15|

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EP00127567|2000-12-15|

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PCT/EP2001/014399|WO2002048145A1|2000-12-15|2001-12-07|Aminotriazolopyridiine derivatives as adenosine receptor ligands|