Benzopyran class III antiarrhythmic agents

• US 5,240,943 A
• Filed: 12/19/1991
• Issued: 08/31/1993
• Est. Priority Date: 12/19/1991
• Status: Expired due to Term

• Current Assignee: GD Searle LLC (Pfizer Inc.)
• Original Assignee: GD Searle LLC (Pfizer Inc.)
• Inventors: Koehler, Konrad F., Russell, Mark A., Desai, Bipinchandra N.
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): Spivack, Phyllis G.
• Application Number:
  US07/810,582
• Time in Patent Office: 621 Days
• Field of Search: 514/320, 546/196
• US Class Current: 514/320
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/14 containing three or more hetero rings

Abstract

The present invention relates to compounds of the formula ##STR1## or a pharmaceutically acceptable salt thereof; wherein n is 0, 1 or 2;

wherein R is H or lower alkyl of 1 to 6 carbon atoms;

wherein X is selected from the group consisting of hydrogen, methane sulfonamide, nitro, cyano, imidazolyl, alkoxy of 1 to 6 carbon atoms and hydroxy; and

wherein Ar is selected from the group consisting of pyridinyl, tetrahydronaphthalenyl, benzofuranyl, and Ph--CH═CH-- and phenyl all optionally substituted by methane sulfonamide, nitro, cyano, or imidazolyl with the proviso that when n is 1, Ar is other then phenyl;

pharmaceutical compositions containing these compounds and a method for treating cardiac arrhythmias in mammals by administering the compositions.

Claims

1. A compound of the formula ##STR15## or a pharmaceutically acceptable salt;

wherein n is 0, 1 or 2;

wherein R is H or lower alkyl of 1 to 6 atoms;

wherein X is selected from the group consisting of hydrogen, methane sulfonamide, nitro, cyano, alkoxy of 1 to 6 carbon atoms and hydroxy; and

wherein Ar is selected from the group consisting of tetrahydronaphthalenyl, Ph--CH═

CH-- and phenyl all optionally substituted by methane sulfonamide, nitro, cyano or imidazolyl, with the proviso that when n is 1Ar is other than phenyl.

2. A compound according to claim 1 wherein n is 1.

3. A compound according to claim 2 wherein Ar is tetrahydronaphthalenyl.

4. A compound according to claim 3 which is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidinyl]-1,2,3,4-tetrahydro-2-naphthalenecarboxamide.

5. A compound according to claim 2 wherein Ar is Ph--CH═

CH--.

6. A compound according to claim 5 which is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidinyl]-3-phenyl-2E-propenamide.

7. A compound according to claim 1 wherein n is 0.

8. A compound according to claim 7 wherein Ar is phenyl.

9. A compound according to claim 8 which is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)methyl]-4-piperidinyl]benzenecarboxamide.

10. A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula ##STR16## or a pharmaceutically acceptable salt thereof;

wherein n is 0, 1 or 2;

wherein R is H or lower alkyl of 1 to 6 carbon atoms;

wherein X is selected from the group consisting of hydrogen, methane sulfonamide, nitro, cyano, alkoxy of 1 to 6 carbon atoms and hydroxy; and

wherein Ar is selected from the group consisting of tetrahydronaphthalenyl, Ph--CH═

CH-- and phenyl all optionally substituted by methane sulfonamide, nitro, cyano or imidazolyl with the proviso that when n is 1, Ar is other than phenyl; and

a pharmaceutically acceptable carrier.

11. A pharmaceutical composition according to claim 10 wherein the compound is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidinyl]-1,2,3,4-tetrahydro-2-naphthalenecarboxamide.

12. A pharmaceutical composition according to claim 10 wherein the compound is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidinyl]-3-phenyl-2E-propenamide.

13. A pharmaceutical composition according to claim 10 wherein the compound is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)methyl]-4-piperidinyl]benzenecarboxamide.

14. A method of treating cardiac arrhythmias in mammals comprising administering to a patient in need of such treatment, a therapeutically effective amount of a compound of the formula ##STR17## or a pharmaceutically acceptable salt thereof;

wherein n is 0, 1 or 2;

wherein R is H or lower alkyl of 1 to 6 carbon atoms;

wherein X is selected from the group consisting of hydrogen, methane sulfonamide, nitro, cyano, alkoxy of 1 to 6 carbon atoms and hydroxy; and

wherein Ar is selected from the group consisting of tetrahydronaphthalenyl, Ph--CH═

CH-- and phenyl all optionally substituted by methane sulfonamide, nitro, cyano or imidazolyl, with the proviso that when n is 1, Ar is other than phenyl.

15. A method of treating cardiac arrhythmias in mammals according to claim 14 wherein the compound is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidinyl]-1,2,3,4-tetrahydro-2-naphthalenecarboxamide.

16. A method of treating cardiac arrhythmias in mammals according to claim 14 wherein the compound is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4-piperidinyl]-3-phenyl-2E-propenamide.

17. A method according to claim 14 wherein the compound is N-[1-[2-(3,4-dihydro-2H-1-benzopyran-4-yl)methyl]-4-piperidinyl]benzenecarboxamide.