N-phenylpyridone type III phosphodiesterases

• US 4,906,628 A
• Filed: 10/14/1986
• Issued: 03/06/1990
• Est. Priority Date: 10/17/1985
• Status: Expired due to Term

• Current Assignee: Smith Kline & French Laboratories Limited Welwyn Garden City Hertfordshire AL7 1EY
• Original Assignee: Smith Kline & French Laboratories Limited (GlaxoSmithKline PLC)
• Inventors: Coates, William J.
• Primary Examiner(s): Berch, Mark L.
• Application Number:
  US06/918,425
• Time in Patent Office: 1,239 Days
• Field of Search: 544/238, 514/252
• US Class Current: 514/252.03
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/10 linked by a carbon chain containing aromatic rings

Abstract

Phosphodiesterase (type III) inhibitors having the formula: ##STR1## which are useful in stimulating cardiac activity and in treating congestive heart failure and bronchoconstriction, pharmaceutical compositions including these inhibitors, and methods of using these compounds to produce phosphodiesterase (type III) inhibition in mammals.

Claims

1. A compound of the formula (1):

##STR39## or a pharmaceutically acceptable salt thereof, wherein;

R¹ is hydrogen, or R¹ and R² together form a bond;

R² is hydrogen or methyl, or R¹ and R² together form a bond; and

R³ is hydrogen.

5. A method for treating congestive heart failure in a host in need thereof by administration of a non-toxic but effective amount of a compound according to claim 1.

6. A pharmaceutical composition according to claim 1 in unit dose form adapted for oral administration.

7. A method for stimulating cardiac activity in a host in need thereof by administration of a non-toxic but effective amount of a compound according to claim 1.

8. A method for effecting bronchodilatation in a host in need thereof by administration of a non-toxic but effective amount of a compound according to claim 1.

9. A compound according to claim 7 which is 5-methyl-6-[4-(4-oxo-1,4-dihydropyridin-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 9 which is (R)-5-methyl-6-[4-(4-oxo-1,4-dihydropyridin-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 9 which is (R)-5-methyl-6-[4-(4-oxo-1,4-dihydropyridin-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone or a pharmaceutically acceptable salt thereof substantially free of the corresponding (S) isomer.

12. A method for effecting phosphodiesterase (type III) inhibition in a host in need thereof by administration of a non-toxic but effective amount of a compound according to claim 1.

13. A pharmaceutical composition having phosphodiesterase (type III) inhibiting activity which comprises an effective amount of a compound according to claim 9 and a pharmaceutically acceptable carrier.

2. A compound according to claim 26 wherein R¹ is hydrogen and R² is hydrogen or methyl, or R¹ and R² together form a bond.

3. A compound according to claim 2 which is:

6-[4-(4-oxo-1,4-dihydropyridin-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone or

6-[4-(4-oxo-1,4-dihydropyridin-1-yl)phenyl]-3(2H)-pyridazinone;

or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition having phosphodiesterase (type III) inhibiting activity which comprises an effective amount of a compound according to claim 2 and a pharmaceutically acceptable carrier.