N-benzylpiperidineisoindolinones

• US 5,053,413 A
• Filed: 09/05/1989
• Issued: 10/01/1991
• Est. Priority Date: 09/05/1989
• Status: Expired due to Fees

• Current Assignee: GD Searle LLC (Pfizer Inc.)
• Original Assignee: GD Searle LLC (Pfizer Inc.)
• Inventors: Desai, Bipinchandra N.
• Primary Examiner(s): Lee, Mary C.
• Assistant Examiner(s): WHITTENBAUGH, ROBERT
• Application Number:
  US07/402,941
• Time in Patent Office: 756 Days
• Field of Search: 546/201, 514/323
• US Class Current: 514/323
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 407/14 containing three or more hetero rings

Abstract

N-benzylpiperidineisoindolinones, which have activity as Class III antiarrhythmic agents, acting by prolonging cardiac action potential repolarization. The invention further provides for compositions incorporating the compounds and methods of their use, as well as providing for pharmaceutically acceptable salts of the compounds.

Claims

1. A compound of the formula ##STR15## the pharmaceutically acceptable salts thereof, and the hydrated forms thereof, wherein R¹ is benzodioxole and R₂ is not present or is alkyl of from one to ten carbon atoms, in which case the N of the piperidinyl ring has a plus charge with the proviso that when R₂ is alkyl of form one to ten carbon atoms R¹ can also be phenyl or phenyl substituted by alkyl of from one to ten carbon atoms.

8. A pharmaceutical composition in unit dose form comprised of a pharmaceutically acceptable carrier in combination with a compound according to claim 1 in an amount effective to treat cardiac arrhythmias in an animal or patient to whom one or more unit doses of said composition are administered.

9. The composition as claimed in claim 8, wherein said compound is 2-[1-(1,3-benzodioxol-5-yl methyl)-4-piperidinyl]-2,3-dihydro-1H-isoindol-1-one, monohydrochloride.

10. The composition as claimed in claim 8, wherein said compound is 1-methyl-4-(2,3-dihydro-1-oxo-1H-isoindol-2-yl)-1-(phenylmethyl)piperidinium iodide.

2. A compound of the formula ##STR16## the pharmaceutically acceptable salts thereof, and the hydrated forms thereof, wherein R¹ is benzodioxole and R₂ is not present or is methyl in which case the N of the piperidine ring has a plus charge with the proviso that when R₂ is methyl R¹ can also be phenyl.

3. The compound as claimed in claim 2, in which the pharmaceutically acceptable salt is a halogen salt.

4. The compound as claimed in claim 3, in which the halogen is chlorine.

5. The compound as claimed in claim 3, in which the halogen is iodine.

6. A compound as claimed in claim 2, of the formula ##STR17##

7. A compound as claimed in claim 2, of the formula ##STR18##

11. A method of regulating cardiac arrhythmias in a mammal comprising administering to such mammal a pharmacologically effective amount of a compound of the formula ##STR19## the pharmaceutically acceptable salts thereof, and the hydrated forms thereof, wherein R₁ is phenyl, phenyl substituted by alkyl of from one to ten carbon atoms, alkyloxyaryl of from one to ten carbon atoms, or benzodioxole and R₂ is not present or is alkyl of from one to ten carbon atoms in which case the N of the piperidinyl ring has a plus charge.

12. A method as claimed in claim 11, wherein said compound is 2-[1-(phenylmethyl)-4-piperidinyl]-2,3-dihydro-1H-isoindol-1-one.

13. A method as claimed in claim 11, wherein said compound is 2-[1-[(4-methyxyphenyl)methyl]-4-piperidinyl]-2,3-dihydro-1H-isoindol-1-one.

14. A method as claimed in claim 11, wherein said compound is 2 [-1 (1,3-benzodioxol-5-yl methyl)-4-piperidinyl]-2,3-dihydro-lH-isoindol-1-one, monohydrochloride.

15. A method as claimed in claim 11, wherein said compound is 1-methyl 4 (2,3-dihydro-oxo lH-isoindol-2-yl)-1-(phenylmethyl) piperidinium iodide.

16. A method of prolonging repolariziation of cardiac cells during a cardiac action potential in a mammal, comprising administering to such mammal of pharmacologically effective amount of a compound of the formula ##STR20## the pharmaceutically acceptable salts thereof, and the hydrated forms thereof, wherein R₁ is phenyl, phenyl substituted by alkyl of from one to ten carbon atoms, alkyloxyaryl of from one to ten carbon atoms, or benzodioxole and R₂ is not present or is alkyl of from one to ten carbon atoms in which case the N of the piperidinyl ring has a plus charge.