PYRIDINE COMPOUNDS AS SODIUM CHANNEL BLOCKERS

• US 20150344465A1
• Filed: 08/12/2015
• Published: 12/03/2015
• Est. Priority Date: 07/16/2010
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Ni, Chiyou, Park, Minnie, Tafesse, Laykea, Kyle, Don J.
• Granted Patent: US 9,765,029 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 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 Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 213/56 Amides
• CPC Class Codes: C07D 213/79 Acids; Esters
• CPC Class Codes: C07D 213/81 Amides; Imides
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

The invention relates to substituted pyridine compounds of Formula I: (I) or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein A¹, X, A², R^1a, R^1b, R^1c, G, and z are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

Claims

1. A compound having the Formula I:

3. The compound of claim 1 having Formula V:

4. The compound of claim 1, wherein A¹ is selected from the group consisting of aryl or heteroaryl, any of which is optionally substituted.

5. The compound of claim 1, wherein A² is absent.

6. The compound of claim 1, wherein X is —

O—

.

7. The compound of claim 1, wherein A¹ is optionally substituted phenyl.

15. The compound of claim 1, wherein R^1b is hydrogen or 1,2-dihydroxyethyl.

17. The compound of claim 1, wherein z is 0.

20. The compound of claim 1, wherein G is selected from the group consisting of:

21. The compound of claim 1, wherein G is selected from the group consisting of:

22. The compound of claim 1, wherein G is:

23. The compound of claim 22, wherein R^7b is selected from the group consisting of alkyl, aryl and heteroaryl, either of which is optionally substituted or NR^11aR^11b.

40. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

46. A method for treating stroke, neuronal damage resulting from head trauma, epilepsy, seizures, neuronal loss following global and focal ischemia, pain, migraine, primary erythromelalgia, paroxysmal extreme pain disorder, cerebellar atrophy, ataxia, mental retardation, a neurodegenerative disorder, manic depression, tinnitus, myotonia, a movement disorder, or cardiac arrhythmia, or providing local anesthesia in a mammal, comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1.

48. The method of claim 46, wherein said method is for treating pain.

49. The method of claim 46, wherein said method is for preemptive or palliative treatment of pain.

50. The method of claim 46, wherein said pain is selected from the group consisting of chronic pain, inflammatory pain, neuropathic pain, acute pain, and surgical pain.

51. A method of modulating sodium channels in a mammal, comprising administering to the mammal at least one compound of claim 1.

53. The method of claim 51, wherein the Na_v1.7 sodium channel is modulated.

60. The compound as claimed in claim 1, wherein the compound is ³H, ¹¹C, or ¹⁴C radiolabeled, or a pharmaceutically acceptable salt, or solvate thereof.

2. (canceled)

8-14. -14. (canceled)

16. (canceled)

18-19. -19. (canceled)

24-37. -37. (canceled)

38. A compound selected from the group consisting of:

39. (canceled)

41-45. -45. (canceled)

47. (canceled)

52. (canceled)

54-59. -59. (canceled)

61-62. -62. (canceled)