N-substituted aminoquinolines as analgesic agents

• US 5,216,165 A
• Filed: 03/20/1992
• Issued: 06/01/1993
• Est. Priority Date: 10/03/1990
• Status: Expired due to Term

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: American Home Products Corporation (Pfizer Inc.)
• Inventors: Musser, John H., Mobilio, Dominick
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): TURNIPSEED, JAMES
• Application Number:
  US07/855,397
• Time in Patent Office: 438 Days
• Field of Search: 546/160
• US Class Current: 546/160
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

There are disclosed compounds of the formula ##STR1## wherein R is hydrogen, halo or trifluoromethyl;

R¹ is hydrogen or X;

R² is hydrogen or X; with the proviso that when R¹ is X, R² is hydrogen, and when R¹ is hydrogen, R² is X;

X is the moiety ##STR2## wherein R³ is hydrogen or lower alkyl;

R⁴ is hydrogen or ##STR3## R⁵ is hydrogen, alkyl of 1-16 carbon atoms, phenyl, phenylloweralkyl or perfluoroloweralkyl;

Y is CO or a bond;

R⁶ is lower alkyl, cycloloweralkyl, arylalkyl, --(CH₂)_m -cycloloweralkyl, ##STR4## or --(CH₂)_o CONR⁸ R⁹ or, in the case when Y is CO, phenyl;

R⁷ is hydrogen or ##STR5## R⁸ and R⁹ are, independently, hydrogen, lower alkyl, cycloloweralkyl or R⁸ and R⁹ together with the nitrogen atom to which they are attached form a 5-8 membered saturated monoazacyclic ring;

m is 1-3;

n is 1-3;

o is 1-10;

and the pharmacologically acceptable salts thereof and, which by virtue of their ability to antagonize bradykinin, are analgesic agents useful in the treatment and management of pain.

Claims

1. A compound having the formula ##STR29## wherein R is hydrogen, halo or trifluoromethyl

R¹ is hydrogen or X;

R² is hydrogen or X;

with the proviso that when R¹ is X, R² is hydrogen, and when R¹ is hydrogen, R² is X;

X is the moiety ##STR30## wherein R³ is hydrogen or lower alkyl;

R⁴ is hydrogen or ##STR31## R⁵ is hydrogen, lower alkyl, phenyl, phenylloweralkyl or perfluoroloweralkyl;

Y is CO or a bond;

R⁶ is lower alkyl, cycloloweralkyl, arylalkyl, --(CH₂)_m -cycloloweralkyl ##STR32## or --(CH₂)_o CONR⁸ R⁹ or, in the case when Y is CO, R⁶ is phenyl;

R⁷ is hydrogen or ##STR33## R⁸ and R⁹ are, independently, hydrogen, lower alkyl or cycloloweralkyl;

m is 1-3;

n is 1-3;

o is 1-10;

and the pharmacologically acceptable salts thereof.

2. A compound of claim 1, having the formula ##STR34## wherein R is hydrogen, halo or trifluoromethyl;

R² is the moiety ##STR35## wherein R⁴ is hydrogen or ##STR36## R⁵ is hydrogen, alkyl of 1-16 carbon atoms, phenyl, phenylloweralkyl or perfluoroloweralkyl;

R⁶ is lower alkyl, cycloloweralkyl, arylalkyl, --(CH₂)_m -cycloloweralkyl or ##STR37## R⁷ is hydrogen or ##STR38## R⁸ and R⁹ are, independently, hydrogen, lower alkyl or cycloloweralkyl;

m is 1-3;

and the pharmacologically acceptable salts thereof.

3. A compound of claim 1, having the name N-[4-[[(1-butyl-4-piperidinyl)amino]methyl]phenyl]-7-chloro-4-quinolinamine.

4. A compound of claim 1, having the name N-(1-butyl-4-piperidinyl)-N-[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]acetamide.

5. A compound of claim 1, having the name N-(1-butyl-4-piperidinyl)-N-[[4-(4-quinolinylamino)phenyl]methyl]acetamide

6. A compound of claim 1, having the name N-(1-butyl-4-piperidinyl)-N-[[4-[7-chloro-4-quinolinyl)amino]phenyl]methyl]benzamide.

7. A compound of claim 1, having the name N-(1-butyl-4-piperidinyl)-N-[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]benzenepropanamide.

8. A compound of claim 1, having the name N-(1-butyl-4-piperidinyl)-N-[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]-2,2,3,3,4,4,4-heptafluorobutanamide.

9. A compound of claim 1, having the name N-(1-butyl-4-piperidinyl)-N-[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]-2,2,2-trifluoroacetamide.

10. A compound of claim 1, having the name N-(1-butyl-4-piperidinyl)-N-[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]butanamide.

11. A compound of claim 1, having the name 4-[[4-[[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]amino]-1-piperidinyl]methyl]-N,N-diethylbenzamide.

12. A compound of claim 1, having the name 7-chloro-N-[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]methyl]phenyl]-4-quinolinamine.

13. A compound of claim 1, having the name N-[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]-N-[1-(phenylmethyl)-4-piperidinyl]butanamide.

14. A compound of claim 1, having the name 4-[[4-[[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl](1-oxobutyl)amino]-1-piperidinyl]methyl]-N,N-diethylbenzamide.

15. A compound of claim 1, having the name 4-[[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]amino]-N,N-diethyl-1-piperidinehexanamide.

16. A compound of claim 1, having the name 4-[[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl](1-oxobutyl)amino]-N,N-diethyl-1-piperidinehexanamide.

17. A compound of claim 1, having the name 1-benzoyl-N-[[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl]-4-piperidinanamine.

18. A compound of claim 1, having the name 4-[[[4-[(7-chloro-4-quinolinyl)amino]phenyl]methyl](1-oxododecyl)amino]-N,N-diethyl-1-piperidinehexanamide.