Substituted pyrazolo[1,5-a] pyridine as tropomyosin receptor kinase (trk) inhibitors

Patent metadata

Field	Value
Publication number	US-2016264572-A1
Application number	US-201615164430-A
Country	US
Kind code	A1
Filing date	May 25, 2016
Priority date	Dec 12, 2011
Publication date	Sep 15, 2016
Grant date	—

Abstract

The present application relates to a series of substituted pyrazolo[1,5-a]pyridine compounds, their use as tropomyosin receptor kinase (Trk) family protein kinase inhibitors, method of making and pharmaceutical compositions comprising such compounds.

First claim

1 . A compound which is

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof or a stereoisomer thereof.

2 . A pharmaceutical composition comprising at least one compound according to claim 1 and at least one pharmaceutically acceptable excipient.

3 . A method of treating conditions, diseases and/or disorders comprising administering a therapeutically effective amount of the compound according to claim 1 , wherein the conditions, diseases and/or disorders are selected from pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, dermatitis, atopic dermatitis, fibrosis, neurodegenerative disease, a disease, disorder, injury relating to dysmyelination or demyelination, infectious diseases, and Trypanosoma Cruzi infection.

4 . A method of treating conditions, diseases and/or disorders comprising administering a therapeutically effective amount of the composition according to claim 2 , wherein the conditions, diseases and/or disorders are selected from pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, dermatitis, atopic dermatitis, fibrosis, neurodegenerative disease, a disease, disorder, injury relating to dysmyelination or demyelination, infectious diseases, and Trypanosoma Cruzi infection.

5 . The pharmaceutical composition according to claim 2 , wherein the composition is in the form of a tablet, a capsule, a cachet, a powder, a granule, a solution, a suspension, an emulsion, a bolus, a lozenge, a suppository, a pessary, a tampon, a cream, a gel, a paste, a foam, a spray, an aerosol, a microcapsule, a liposome, a transdermal patch, a pastille, a paste, or a mouthwash.

6 . The compound according to claim 1 , selected from

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof or a stereoisomer thereof.

7 . A pharmaceutical composition comprising at least one compound according to claim 6 and at least one pharmaceutically acceptable excipient.

8 . The pharmaceutical composition according to claim 7 , wherein the composition is in the form of a tablet, a capsule, a cachet, a powder, a granule, a solution, a suspension, an emulsion, a bolus, a lozenge, a suppository, a pessary, a tampon, a cream, a gel, a paste, a foam, a spray, an aerosol, a microcapsule, a liposome, a transdermal patch, a pastille, a paste, or a mouthwash.

9 . A method of treating conditions, diseases and/or disorders comprising administering a therapeutically effective amount of the compound according to claim 6 , wherein the conditions, diseases and/or disorders are selected from pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, dermatitis, atopic dermatitis, fibrosis, neurodegenerative disease, a disease, disorder, injury relating to dysmyelination or demyelination, infectious diseases, and Trypanosoma Cruzi infection.

10 . A method of treating conditions, diseases and/or disorders comprising administering a therapeutically effective amount of the composition according to claim 8 , wherein the conditions, diseases and/or disorders are selected from pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, dermatitis, atopic dermatitis, fibrosis, neurodegenerative disease, a disease, disorder, injury relating to dysmyelination or demyelination, infectious diseases, and Trypanosoma Cruzi infection.

11 . A method of inhibiting tropomyosin receptor kinase A (TrkA) in a patient comprising administering to said patient a therapeutically effective amount of the compound according to claim 1 .

12 . The compound according to claim 1 having TrkA inhibitory activity using TR-FRET assay of less than about 1 μM.

13 . The compound according to claim 1 having TrkA inhibitory activity using TR-FRET assay of less than about 100 nm.

14 . The compound according to claim 1 having TrkA inhibitory activity using TR-FRET assay of less than about 50 nM.

15 . A compound which is

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof or a stereoisomer thereof.

Assignees

• Dr Reddys Laboratories Ltd

Inventors

• Sasmal Pradip Kumar
• Ahmed Shahadat
• Tehim Ashok
• Paradkar Vidyadhar
• Dattatreya Prasanna M
• Mavinahalli Nanjegowda Jagadeesh

Classifications

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/06

  Antimigraine agents · CPC title