Tropomyosin-related kinase inhibitors

• US 9,328,096 B2
• Filed: 05/06/2015
• Issued: 05/03/2016
• Est. Priority Date: 05/07/2014
• Status: Expired due to Fees

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Bagal, Sharanjeet Kaur, Cui, Jingrong Jean, Lunney, Elizabeth Ann, McAlpine, Indrawan James, Nagata, Asako, Ninkovic, Sacha, Omoto, Kiyoyuki, Skerratt, Sarah Elizabeth, Storer, Robert Ian, Warmus, Joseph Scott, Greasley, Samantha Elizabeth
• Primary Examiner(s): Anders, Janet L
• Assistant Examiner(s): CARCANAGUE, DANIEL R
• Application Number:
  US14/705,272
• Publication Number:
  US 20150322043A1
• Time in Patent Office: 363 Days
• Field of Search: 514/171
• US Class Current: 1/1
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

The present invention relates to compounds of Formula I

and their pharmaceutically acceptable salts, wherein the substituents are as described herein, and their use in medicine, in particular as TrkA antagonists.

Claims

1. 5-(2,4-dichloro-5-(pyridin-2-yl)benzamido)-N-(2-hydroxy-2-methylpropyl)-1-phenyl-1H-pyrazole-3-carboxamide, or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 1, and a pharmaceutically acceptable carrier.

4. A method of treatment of pain in a mammal, comprising treating said mammal with an effective amount of a compound or a pharmaceutically acceptable salt thereof, as defined in claim 1.

2. 5-{[2,4-dichloro-5-(3-fluoropyridin-2-yl)benzoyl]amino}-N-(2-hydroxy-2-methylpropyl)-1-phenyl-1H-pyrazole-3-carboxamide, or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 2, and a pharmaceutically acceptable carrier.

16. A method of treatment of pain in a mammal, comprising treating said mammal with an effective amount of a compound or a pharmaceutically acceptable salt thereof, as defined in of claim 2.

5. N-((1H-1,2,3-triazol-4-yl)methyl)-5-(2-chloro-4-fluoro-5-(pyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxamide, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 5, and a pharmaceutically acceptable carrier.

17. A method of treatment of pain in a mammal, comprising treating said mammal with an effective amount of a compound or a pharmaceutically acceptable salt thereof, as defined in of claim 5.

6. 2,4-dichloro-5-(3-fluoropyridin-2-yl)-N-{3-[(3-oxopiperazin-1-yl)carbonyl]-1-phenyl-1H-pyrazol-5-yl}benzamide, or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 6, and a pharmaceutically acceptable carrier.

18. A method of treatment of pain in a mammal, comprising treating said mammal with an effective amount of a compound or a pharmaceutically acceptable salt thereof, as defined in of claim 6.

7. 5-{[2,4-dichloro-5-(pyridin-2-yl)benzoyl]amino}-N-(trans-4-hydroxycyclohexyl)-1-phenyl-1H-pyrazole-3-carboxamide, or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 7, and a pharmaceutically acceptable carrier.

19. A method of treatment of pain in a mammal, comprising treating said mammal with an effective amount of a compound or a pharmaceutically acceptable salt thereof, as defined in of claim 7.

8. N-(3-{[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]carbonyl}-1-phenyl-1H-pyrazol-5-yl)-2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamide, or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 8, and a pharmaceutically acceptable carrier.

20. A method of treatment of pain in a mammal, comprising treating said mammal with an effective amount of a compound or a pharmaceutically acceptable salt thereof, as defined in of claim 8.

9. N-(3-amino-2,2-difluoropropyl)-5-{[2-chloro-4-fluoro-5-(3-fluoropyridin-2-yl)benzoyl]amino}-1-phenyl-1H-pyrazole-3-carboxamide, or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 9, and a pharmaceutically acceptable carrier.

21. A method of treatment of pain in a mammal, comprising treating said mammal with an effective amount of a compound or a pharmaceutically acceptable salt thereof, as defined in of claim 9.