Heterocyclic derivatives as modulators of ion channels

• US 7,846,954 B2
• Filed: 07/01/2009
• Issued: 12/07/2010
• Est. Priority Date: 07/01/2008
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Stamos, Dean, Numa, Mehdi Michel Djamel, Grootenhuis, Peter D. J., Whitney, Tara, Zimmermann, Nicole, Anderson, Corey Don
• Primary Examiner(s): McKane; Joseph
• Assistant Examiner(s): Loewe; Sun Jae Y
• Application Number:
  US12/495,880
• Publication Number:
  US 20100004300A1
• Time in Patent Office: 524 Days
• Field of Search: None
• US Class Current: 514/370
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• 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 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings

Abstract

The present invention relates to heterocyclic derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

Claims

1. A compound of formula I:

2. The compound of claim 1, wherein R is halo.

3. The compound of claim 1, wherein R₁ is halo.

4. The compound of claim 1, wherein R₁ is C1-C6 aliphatic.

5. The compound of claim 1, wherein m is 0.

6. The compound of claim 1, wherein m is 2.

7. The compound of claim 1, wherein n is 0.

8. The compound of claim 1, wherein n is 1.

9. The compound of claim 1, wherein n is 2.

10. The compound of claim 1, wherein R is F.

11. The compound of claim 1, wherein R₁ is Cl.

12. The compound of claim 1, wherein R₁ is F.

13. The compound of claim 1, wherein R₁ is methyl.

14. The compound of claim 1, wherein m and n are 0.

15. The compound of claim 1, wherein m is 0 and n is 1.

16. The compound of claim 1, wherein m is 0 and n is 2.

17. The compound of claim 1, wherein m is 0, n is 1, and R₁ is Cl.

18. The compound of claim 1, wherein m is 0, n is 1, and R₁ is F.

19. The compound of claim 1, wherein m is 0, n is 2, and R₁ is Cl.

20. The compound of claim 1, wherein m is 0, n is 2, and R₁ is Cl or Me.

21. The compound of claim 1, wherein m is 2, R is F, and n is 2.

22. The compound of claim 1, wherein m is 2, R is F, n is 2, and R₁ is Cl.

23. The compound of claim 1, of formula Ia, Ib, Ic, Id, or Ie:

24. The compound of claim 1, wherein the compound is selected from

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