Fused heterocyclic compounds as ion channel modulators

Patent metadata

Field	Value
Publication number	US-9371329-B2
Application number	US-201414274422-A
Country	US
Kind code	B2
Filing date	May 9, 2014
Priority date	Jul 27, 2009
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

Abstract

The present invention relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I:

wherein W 1 , W 2 , W 3 , R 1 , Q, X 1 , X 2 and X 3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

First claim

What is claimed is:

1. A compound selected from the group consisting of:
6-[4-(trifluoromethoxy)phenyl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;
6-(4-phenoxyphenyl)-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;
3-(difluoromethyl)-6-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[4,3-b]pyridazine;
3-(difluoromethyl)-6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazine;
6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazine;
6-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[4,3-b]pyridazine;
6-[2-methyl-4-(trifluoromethoxy)phenyl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;
6-(4-phenoxyphenyl)-3-(2,2,2-trifluoroethyl)[1,2,4]triazolo[4,3-b]pyridazine;
6-(4-phenoxyphenyl)-3-(propan-2-yl)[1,2,4]triazolo[4,3-b]pyridazine;
6-[2-methyl-4-(trifluoromethoxy)phenyl]-3-(propan-2-yl)[1,2,4]triazolo[4,3-b]pyridazine;
3-tert-butyl-6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazine;
3-tert-butyl-6-[4-(2,2,2-trifluoroethoxy)phenyl][1,2,4]triazolo[4,3-b]pyridazine;
3-ethyl-6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazine;
3-cyclopropyl-6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazine;
4-[6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]benzonitrile;
4-{6-[2-methyl-4-(trifluoromethoxy)phenyl][1,2,4]triazolo[4,3-b]pyridazin-3-yl}benzonitrile;
4-{6-[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[4,3-b]pyridazin-3-yl}benzonitrile;
3-(1-methyl-1H-pyrazol-4-yl)-6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazine;
4-[6-(4-methoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]benzonitrile;
3-[6-(4-methoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]benzonitrile;
3-[4-(methylsulfonyl)phenyl]-6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazine;
3-{6-[6-(morpholin-4-yl)pyridin-3-yl][1,2,4]triazolo[4,3-b]pyridazin-3-yl}benzonitrile,
6-(4-phenoxyphenyl)-3-[4-(2H-tetrazol-5-yl)phenyl][1,2,4]triazolo[4,3-b]pyridazine;
3-[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]benzonitrile;
2-[6-(4-phenoxyphenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]propan-2-ol;
3,6-bis[4-(trifluoromethoxy)phenyl][1,2,4]triazolo[4,3-b]pyridazine;
3-{6-[2-methyl-4-(trifluoromethoxy)phenyl][1,2,4]triazolo[4,3-b]pyridazin-3-yl}benzonitrile;
6-(3,5-difluoro-4-phenoxyphenyl)-3-(propan-2-yl)[1,2,4]triazolo[4,3-b]pyridazine;
3-(propan-2-yl)-6-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl][1,2,4]triazolo[4,3-b]pyridazine;
6-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;
6-(3,5-difluoro-4-phenoxyphenyl)-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;
6-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;
6-[4-(4-chlorophenoxy)phenyl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;
3-(difluoromethyl)-6-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl][1,2,4]triazolo[4,3-b]pyridazine; and
3-(difluoromethyl)-6-[3-fluoro-4-(trifluoromethoxy)phenyl][1,2,4]triazolo[4,3-b]pyridazine.

2. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

Assignees

• Corkey Britton
• Elzein Elfatih
• Jiang Robert
• Kalla Rao
• Kobayashi Tetsuya
• Koltun Dmitry
• Li Xiaofen
• Notte Gregory
• Parkhill Eric
• Perry Thao
• Zablocki Jeff
• Gilead Sciences Inc

Inventors

• Corkey Britton
• Elzein Elfatih
• Jiang Robert
• Kalla Rao
• Kobayashi Tetsuya
• Koltun Dmitry
• Li Xiaofen
• Notte Gregory
• Parkhill Eric
• Perry Thao
• Zablocki Jeff

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · 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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title