Back to results
US 5,294,621 AGranted
Thieno tetrahydropyridines useful as class III antiarrhythmic agents
AssigneeOrtho Pharmaceutical Corporation
InventorRonald K. Russell
Life of this patent
Estimating the term…
Abstract
This invention relates to thieno tetrahydropyridine and isoquinoline derivative compounds which are useful as antiarrhythmic agents, pharmaceutical compositions comprising such compounds, novel intermediates for their preparation and their methods of use. More particularly these thieno tetrahydropyridine and isoquinoline derivative compounds have been demonstrated to increase the effective refractory period (ERP) of isolated perfused cardiac tissue in vitro.
Claims17
A compound of the following formula:
- ##STR36## where Ar' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR37## R.sub.1 is hydrogen or C.sub.1 -C.sub.3 alkyl;
- R.sub.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 branched chain alkyl;
- R.sub.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 branched chain alkyl, aryl or substituted aryl wherein the aryl substituents are C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkoxy;
- R.sub.4 is hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.3 -C.sub.7 branched chain alkyl, halogen, C.sub.1 -C.sub.3 alkoxy, nitro, amino, imidazole, cyano, CO.sub.2 R.sub.1, SO.sub.2 R.sub.1, CF.sub.3, NHCOR.sub.8, NR.sub.7 SO.sub.2 R.sub.8, CH.sub.2 SO.sub.2 R.sub.1, CH.sub.2 PO(OR.sub.1).sub.2 or CH.sub.2 -imidazole;
- X is (CH.sub.2).sub.m NR.sub.7 CO, (CH.sub.2).sub.m NR.sub.7 SO.sub.2 or (CH.sub.2).sub.m NHCH.sub.2 ;
- ##STR38## R.sub.5 is hydrogen, halogen or nitro;
- R.sub.7 is hydrogen or C.sub.1 -C.sub.3 alkyl;
- R.sub.8 is hydrogen, CF.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.5 branched chain alkyl, aryl or substituted aryl;
- m is 2-4;
- and
- when R.sub.1 is alkyl and R.sub.2 is hydrogen and when R.sub.1 /R.sub.3 or R.sub.2 /R.sub.3 are both alkyl;
- R.sub.1 /R.sub.3 is cis or trans and R.sub.2 /R.sub.3 is cis or trans ##STR39##
9 more elements
A compound of the following formula:
- ##STR40## where Ar' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR41## R.sub.1 is hydrogen or C.sub.1 -C.sub.3 alkyl;
- R.sub.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 branched chain alkyl;
- R.sub.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 branched chain alkyl, aryl or substituted aryl wherein the aryl substituents are C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkoxy;
- R.sub.4 is hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.3 -C.sub.7 branched chain alkyl, halogen, C.sub.1 -C.sub.3 alkoxy, nitro, amino, imidazole, cyano, CO.sub.2 R.sub.1, SO.sub.2 R.sub.1, CF.sub.3, NHCOR.sub.8, NR.sub.7 SO.sub.2 R.sub.8, CH.sub.2 SO.sub.2 R.sub.1, CH.sub.2 PO(OR.sub.1).sub.2 or CH.sub.2 -imidazole;
- X is (CH.sub.2).sub.m NR.sub.7 CO, (CH.sub.2).sub.m NR.sub.7 SO.sub.2 or (CH.sub.2).sub.m NHCH.sub.2 ;
- ##STR42## R.sub.5 is hydrogen, halogen or nitro;
- R.sub.7 is hydrogen or C.sub.1 -C.sub.3 alkyl;
- R.sub.8 is hydrogen, CF.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.5 branched chain alkyl, aryl or substituted aryl;
- m is 2-4;
- and
- when R.sub.1 is alkyl and R.sub.2 is hydrogen and when R.sub.1 /R.sub.3 or R.sub.2 /R.sub.3 are both alkyl;
- R.sub.1 /R.sub.3 is cis or trans and R.sub.2 /R.sub.3 is cis or trans, ##STR43##
9 more elements
A compound of the following formula:
- ##STR44## where Ar' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR45## R.sub.1 is hydrogen or C.sub.1 -C.sub.3 alkyl;
- R.sub.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 branched chain alkyl;
- R.sub.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 branched chain alkyl, aryl or substituted aryl wherein the aryl substituents are C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkoxy;
- R.sub.4 is hydrogen, C.sub.1 -C.sub.5 alkyl, C.sub.3 -C.sub.7 branched chain alkyl, halogen, C.sub.1 -C.sub.3 alkoxy, nitro, amino, imidazole, cyano, CO.sub.2 R.sub.1, SO.sub.2 R.sub.1, CF.sub.3, NHCOR.sub.8, NR.sub.7 SO.sub.2 R.sub.8, CH.sub.2 SO.sub.2 R.sub.1, CH.sub.2 PO(OR.sub.1).sub.2 or CH.sub.2 -imidazole;
- X is CH.sub.2, (CH.sub.2).sub.n, (CH.sub.2).sub.n O, (CH.sub.2).sub.m NR.sub.7 CO, (CH.sub.2).sub.m NR.sub.7 SO.sub.2, (CH.sub.2).sub.m NHCH.sub.2, ##STR46## n is 2-5;
- R.sub.5 is hydrogen, halogen or nitro;
- R.sub.7 is hydrogen or C.sub.1 -C.sub.3 alkyl;
- R.sub.8 is hydrogen, CF.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.5 branched chain alkyl, aryl or substituted aryl;
- m is 2-4;
- and,
- when R.sub.1 is alkyl and R.sub.2 is hydrogen and when R.sub.1 /R.sub.3 or R.sub.2 /R.sub.3 are both alkyl;
- R.sub.1 /R.sub.3 is cis or trans and R.sub.2 /R.sub.3 is cis or trans, ##STR47##
9 more elements
The compound:
- cis-7-Butyl-4,5,6,7-tetrahydro-5-methyl-6-[2-(4-methanesulfonamidobenzamido )ethyl]thieno[2,3-c]pyridine and the intermediates 2-[3-(cis-4,5,6,7-tetrahydro-5,7-dimethylthieno[2,3-c]pyridin-6-yl)propyl] -1H-isoindole-1,3-dione and 2-[4-(cis-4,5,6,7-tetrahydro-5,7-dimethylthieno[2,3-c]pyridine-6-yl)butyl] -1H-isoindole-1,3-dione.
Dependencies are inferred from the claim text.