Thieno tetrahydropyridines useful as class III antiarrhythmic agents
First Claim
Patent Images
1. A compound of the following formula:
- ##STR36## where Ar'"'"' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR37## R1 is hydrogen or C1 -C3 alkyl;
R2 is hydrogen, C1 -C6 alkyl, C3 -C7 branched chain alkyl;
R3 is hydrogen, C1 -C6 alkyl, C3 -C7 branched chain alkyl, aryl or substituted aryl wherein the aryl substituents are C1 -C6 alkyl or C1 -C6 alkoxy;
R4 is hydrogen, C1 -C5 alkyl, C3 -C7 branched chain alkyl, halogen, C1 -C3 alkoxy, nitro, amino, imidazole, cyano, CO2 R1, SO2 R1, CF3, NHCOR8, NR7 SO2 R8, CH2 SO2 R1, CH2 PO(OR1)2 or CH2 -imidazole;
X is (CH2)m NR7 CO, (CH2)m NR7 SO2 or (CH2)m NHCH2 ;
##STR38## R5 is hydrogen, halogen or nitro;
R7 is hydrogen or C1 -C3 alkyl;
R8 is hydrogen, CF3, C1 -C4 alkyl, C3 -C5 branched chain alkyl, aryl or substituted aryl;
m is 2-4; and
when R1 is alkyl and R2 is hydrogen and when R1 /R3 or R2 /R3 are both alkyl;
R1 /R3 is cis or trans and R2 /R3 is cis or trans ##STR39##
1 Assignment
0 Petitions
Accused Products
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.
-
Citations
18 Claims
-
1. A compound of the following formula:
- ##STR36## where Ar'"'"' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR37## R1 is hydrogen or C1 -C3 alkyl;
R2 is hydrogen, C1 -C6 alkyl, C3 -C7 branched chain alkyl;R3 is hydrogen, C1 -C6 alkyl, C3 -C7 branched chain alkyl, aryl or substituted aryl wherein the aryl substituents are C1 -C6 alkyl or C1 -C6 alkoxy; R4 is hydrogen, C1 -C5 alkyl, C3 -C7 branched chain alkyl, halogen, C1 -C3 alkoxy, nitro, amino, imidazole, cyano, CO2 R1, SO2 R1, CF3, NHCOR8, NR7 SO2 R8, CH2 SO2 R1, CH2 PO(OR1)2 or CH2 -imidazole; X is (CH2)m NR7 CO, (CH2)m NR7 SO2 or (CH2)m NHCH2 ;
##STR38## R5 is hydrogen, halogen or nitro;
R7 is hydrogen or C1 -C3 alkyl;R8 is hydrogen, CF3, C1 -C4 alkyl, C3 -C5 branched chain alkyl, aryl or substituted aryl; m is 2-4; and when R1 is alkyl and R2 is hydrogen and when R1 /R3 or R2 /R3 are both alkyl;
R1 /R3 is cis or trans and R2 /R3 is cis or trans ##STR39## - View Dependent Claims (2, 3, 5, 6, 8, 10, 12, 13, 14, 15, 16, 17, 18)
- ##STR36## where Ar'"'"' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR37## R1 is hydrogen or C1 -C3 alkyl;
-
4. 5,6,7-Tetrahydro-5-[2-(4-nitrobenzamido)ethyl]thieno[3,2-c]pyridine
cis-4,5,6,7-Tetrahydro-4,6-dimethyl-5-[2-(4-nitrobenzamido)ethyl]thieno[3,2-c]pyridine; -
cis-2-Chloro-4,5,6,7-tetrahydro-4,6-dimethyl-5-[2-(4-nitrobenzamido)ethyl]thieno[3,2-c[pyridine; cis-2-Bromo-4,5,6,7-tetrahydro-4,6-dimethyl-5-[2-(4-nitrobenzamido)ethyl]thieno[3,2-c]pyridine; cis-4,5,6,7-Tetrahydro-4,6-dimethyl-2-nitro-5-[2-(4-nitrobenzamido)ethyl]thieno[3,2-c]pyridine; cis-4,5,6,7-Tetrahydro-5,7-dimethyl-6-[2-(4-methanesulfonamidobenzamido)ethyl]thieno[3,2-c]pyridine; trans-4,5,6,7-Tetrahydro-5,7-dimethyl-6-[2-(4-methanesulfonamidobenzamido)ethyl]thieno[3,2-c]pyridine; cis-2-Bromo-4,5,6,7-tetrahydro-5-[2-(4-methanesulfonamidobenzamido)ethyl]-4,6-dimethylthieno[3,2-c]pyridine; cis-4,5,6,7-Tetrahydro-5-[2-(4-methanesulfonylaminophenoxy)-ethyl]-4,6-dimethylthieno[3,2-c]pyridine; cis-1-Chloro-4,5,6,7-tetrahydro-4,6-dimethyl-5-[2-(4-nitrobenzamido)ethyl]thieno[3,4-c[pyridine; trans-1-Chloro-4,5,6,7-tetrahydro-4,6-dimethyl-5-[2-(4-nitrobenzamido)ethyl]thieno[3,4-c[pyridine; cis-2-Chloro-4,5,6,7-tetrahydro-4,6-dimethyl-5-[2-(4-methanesulfonamidobenz
-
-
7. A compound of the following formula:
- ##STR40## where Ar'"'"' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR41## R1 is hydrogen or C1 -C3 alkyl;
R2 is hydrogen, C1 -C6 alkyl, C3 -C7 branched chain alkyl;R3 is hydrogen, C1 -C6 alkyl, C3 -C7 branched chain alkyl, aryl or substituted aryl wherein the aryl substituents are C1 -C6 alkyl or C1 -C6 alkoxy; R4 is hydrogen, C1 -C5 alkyl, C3 -C7 branched chain alkyl, halogen, C1 -C3 alkoxy, nitro, amino, imidazole, cyano, CO2 R1, SO2 R1, CF3, NHCOR8, NR7 SO2 R8, CH2 SO2 R1, CH2 PO(OR1)2 or CH2 -imidazole; X is (CH2)m NR7 CO, (CH2)m NR7 SO2 or (CH2)m NHCH2 ;
##STR42## R5 is hydrogen, halogen or nitro;
R7 is hydrogen or C1 -C3 alkyl;R8 is hydrogen, CF3, C1 -C4 alkyl, C3 -C5 branched chain alkyl, aryl or substituted aryl; m is 2-4; and when R1 is alkyl and R2 is hydrogen and when R1 /R3 or R2 /R3 are both alkyl;
R1 /R3 is cis or trans and R2 /R3 is cis or trans, ##STR43##
- ##STR40## where Ar'"'"' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR41## R1 is hydrogen or C1 -C3 alkyl;
-
9. A compound of the following formula:
- ##STR44## where Ar'"'"' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR45## R1 is hydrogen or C1 -C3 alkyl;
R2 is hydrogen, C1 -C6 alkyl, C3 -C7 branched chain alkyl;R3 is hydrogen, C1 -C6 alkyl, C3 -C7 branched chain alkyl, aryl or substituted aryl wherein the aryl substituents are C1 -C6 alkyl or C1 -C6 alkoxy; R4 is hydrogen, C1 -C5 alkyl, C3 -C7 branched chain alkyl, halogen, C1 -C3 alkoxy, nitro, amino, imidazole, cyano, CO2 R1, SO2 R1, CF3, NHCOR8, NR7 SO2 R8, CH2 SO2 R1, CH2 PO(OR1)2 or CH2 -imidazole; X is CH2, (CH2)n, (CH2)n O, (CH2)m NR7 CO, (CH2)m NR7 SO2, (CH2)m NHCH2, ##STR46## n is 2-5;
R5 is hydrogen, halogen or nitro;R7 is hydrogen or C1 -C3 alkyl; R8 is hydrogen, CF3, C1 -C4 alkyl, C3 -C5 branched chain alkyl, aryl or substituted aryl; m is 2-4; and
,when R1 is alkyl and R2 is hydrogen and when R1 /R3 or R2 /R3 are both alkyl;
R1 /R3 is cis or trans and R2 /R3 is cis or trans, ##STR47##
- ##STR44## where Ar'"'"' is selected from the group consisting of pyridine, thiophene, furan, pyrrole or ##STR45## R1 is hydrogen or C1 -C3 alkyl;
-
11. 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.
Specification
-
- Resources
Litigation Campaign Assessment
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeOrtho Pharmaceutical Corporation (Johnson & Johnson)
-
Original AssigneeOrtho Pharmaceutical Corporation (Johnson & Johnson)
-
InventorsRussell, Ronald K.
-
Primary Examiner(s)Dentz, Bernard
-
Application NumberUS07/958,197Time in Patent Office524 DaysField of Search546/114, 514/301US Class Current514/301CPC Class CodesC07D 217/04 with hydrocarbon or substit...C07D 495/04 Ortho-condensed systems
