Pyridine compounds as sodium channel blockers

• US 9,765,029 B2
• Filed: 08/12/2015
• Issued: 09/19/2017
• Est. Priority Date: 07/16/2010
• Status: Expired due to Fees

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Kyle, Don, Ni, Chiyou, Park, Minnie, Tafesse, Laykea
• Primary Examiner(s): Klinkel, Kortney L
• Assistant Examiner(s): LEE, WILLIAM Y
• Application Number:
  US14/824,319
• Publication Number:
  US 20150344465A1
• Time in Patent Office: 769 Days
• Field of Search: None
• 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 of Formula V

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

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

O—

.

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

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

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

8. A method for treating pain in a mammal, comprising administering to a mammal in need of such treatment an effective amount of a compound of claim 1.

9. The method of claim 8, wherein said method is for preemptive or palliative treatment of pain.

10. The method of claim 8, wherein said pain is selected from the group consisting of chronic pain, inflammatory pain, neuropathic pain, acute pain, and surgical pain.

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

12. The method of claim 11, wherein the Nav1.7 sodium channel is blocked.

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

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

(CR²R³)_m—

, and m is 0.

6. A compound selected from the group consisting of: