Nitrogen-containing spirocycles

• US 5,633,247 A
• Filed: 07/05/1995
• Issued: 05/27/1997
• Est. Priority Date: 12/08/1989
• Status: Expired due to Fees

• Current Assignee: Merck & Co., Inc.
• Original Assignee: Merck & Co., Inc.
• Inventors: Claremon, David A., Baldwin, John J., Selnick, Harold G., Ponticello, Gerald S., Remy, David C., Elliott, Jason M.
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): COVINGTON, RAYMOND K
• Application Number:
  US08/498,525
• Time in Patent Office: 692 Days
• Field of Search: 514/210, 514/212, 514/278, 514/306, 514/409, 540/367, 540/466, 540/543, 546/17, 548/409, 548/411
• US Class Current: 514/210.2
• CPC Class Codes: C07D 221/20 Spiro-condensed ring systems
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 471/10 Spiro-condensed systems
• CPC Class Codes: C07D 491/10 Spiro-condensed systems
• CPC Class Codes: C07D 495/10 Spiro-condensed systems
• CPC Class Codes: C07D 513/10 Spiro-condensed systems

Abstract

Spirocycles of general structural formula: ##STR1## are Class III antiarrhythmic agents.

Claims

1. A compound of structural formula I:

##STR366## wherein;

X and Y are independently --O--, CHOH, --(CH₂)--;

Z is --O--;

M is ##STR367## R is C_1-6 alkyl;

R¹, R² and R³ are independently H, --NHSO₂ (C_1-6 alkyl), --CN;

B is a ring of 5 to 8 members; and

Ar is a single or fused ring carbocyclic or heterocyclic ring system containing up to 4 heteroatoms;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 which is N-{1'"'"'-(6-cyano-1,2,3,4-tetrahydro-2-napthalenyl)-3,4-dihydro-4-hydroxyspiro[2H-1-benzopyran-2,4'"'"'-piperidin-yl]methanesulfonamide.

5. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 1.

6. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 2.

8. A method for treating arrhythmia which comprises administering to a patient in need thereof a therapeutically effective amount of a composition of claim 5.

9. A method for treating arrhythmia which comprises administering to a patient in need thereof a therapeutically effective amount of a composition of claim 6.

3. A compound which is N-{1'"'"'-(6-cyano-1,2,3,4-tetrahydro-2-napthalenyl)-3,4-dihydo-4-hydroxyspiro[2H-1-benzopyran-2,4'"'"'-piperidinyl]methanesulfonamide, in the (R,R) form, the (R,S) form the (S,R) form, or the (S,S) form, or mixtures thereof, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 3, which is in the (R,R) form.

7. A pharmaceutical composition comprising a pharmaceutical carrier and dispersed therein, a therapeutically effective amount of a compound of claim 3.

10. A method for treating arrhythmia which comprises administering to a patient in need thereof a therapeutically effective amount of a composition of claim 7.