Fused heterocyclic compounds as ion channel modulators
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.
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.