Tetralone derivatives as antiarrhythmic agents

• US 6,048,877 A
• Filed: 01/20/1998
• Issued: 04/11/2000
• Est. Priority Date: 02/21/1997
• Status: Expired due to Term

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Ahmad, Saleem, Stein, Philip D., Atwal, Karnail S., Ferrara, Francis N.
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US09/009,812
• Time in Patent Office: 812 Days
• Field of Search: 544/359, 544/361, 544/368, 544/380, 546/15, 546/16, 546/79, 546/203, 546/205, 546/285, 548/407, 548/427, 548/528, 548/530, 548/579, 564/47, 564/173, 564/180, 568/326, 568/328, 568/330, 514/229.5, 514/247, 514/255, 514/278, 514/319, 514/325, 514/326, 514/357, 514/408, 514/409, 514/411, 514/423, 514/595, 514/617, 514/623, 514/682, 514/684
• US Class Current: 514/319
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: C07C 217/74 with rings other than six-membered aromatic rings being part of the carbon skeleton
• CPC Class Codes: C07C 235/78 the carbon skeleton containing rings
• CPC Class Codes: C07C 235/82 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 2602/08 the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07D 211/14 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 295/096 with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/116 with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
• CPC Class Codes: C07D 295/155 with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/185 from aliphatic carboxylic acids
• CPC Class Codes: C07D 401/08 linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

Tetralone derivatives of the formula ##STR1## where R¹ is halo, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, (aryl)alkenyl, (aryl)alkynyl, alkoxy, O-alkenyl, O-aryl, O-alkyl(heterocyclo), COO-alkyl,alkanoyl, CO-amino, CO-substituted amino, alkyl-CO-amino, alkyl-CO-substituted amino, NHCO-alkyl, NHCO-aryl, NHCO-alkyl(heterocyclo), N(alkyl)CO-alkyl, N(alkyl)CO-aryl, N(alkyl)CO-heterocyclo, N(alkyl)CO-alkyl(heterocyclo);

R² is hydrogen, alkyl, halo, aryl, alkoxy, amino, substituted amino;

R³ is oxo, hydroxy, alkoxy, O--COalkyl, --O--COaryl, --O--COheterocyclo, NOH, NO-alkyl, N-amino, N-substituted amino, N-NHCONHalkyl, N-NHSO₂ alkyl, N-NHSO₂ aryl, amino, substituted amino, NHCO-alkyl, NHCO-aryl, NHCO-heterocyclo, spiroheterocyclo;

R⁴ is hydrogen, alkyl, alkyl(COalkyl), alkyl(COOalkyl); or

R³ and R⁴ taken together with the atoms to which they are attached form a five- to seven-membered ring which can contain up to three heteroatoms selected from oxygen, nitrogen and sulfur;

R⁵ is hydrogen, alkyl, alkenyl, alkyl(heterocyclo), alkyl-NHCO(alkyl), alkyl-NHCO(aryl), alkyl-NHCO(heterocyclo), alkyl-NHCO(alkylheterocyclo); and

n is an integer of 0 to 2. These compounds have been found to be useful in the treatment of arrhythmia.

Claims

1. A method of treating cardiac arrhythmia which comprises administering to a mammal in need thereof an effective amount of a compound of the formula I ##STR266## where R¹ is O-alkyl(aryl), CONH-alkyl, CONH-alkyl(aryl) or CONHalkyl(cycloalkyl)

R² is hydrogen;

R³ is oxo, hydroxy, alkoxy, or NOH;

R⁴ is hydrogen or alkyl;

R⁵ is alkyl(heterocyclo) or alkyl(substituted amino); and

n is an integer of 0 to 2

with the proviso that where R³ is oxo, or hydroxy and R¹ is phenylalkyloxy, then R⁵ is alkyl(heterocyclo).

12. The method as defined in claim 1 where in the compound employed R⁵ is heterocycloalkyl wherein heterocyclo is substituted with alkyl, aryl, alkylthio, alkoxy, halo, nitro, keto, cyano, hydroxy, azo, oxo, thiazo, amino, substituted amino, carboxylic acid, or carboxylic ester, or alkoxy further substituted with a carboxylic acid or a 5- to 8-membered ring optionally containing 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur, optionally substituted with alkyl or halogen.

13. The method as defined in claim 1 where in the compound employed R⁵ is piperidinylalkyl.

14. The method as defined in claim 1 where in the compound employed R⁵ is 4-phenyl-1-piperidinylalkyl.

16. The method as defined in claim 1 where in the compound employed R¹ is arylalkyloxy.

17. The method as defined in claim 1 where in the compound employed R¹ is 2-phenylphenylmethoxy and R⁵ is 4-phenyl-1-piperidinylethyl, and R² is H, R³ is oxo and n is 1.

18. The method as defined in claim 1 where the compound employed has the structure

2. A compound of formula I ##STR267## where R¹ is O-alkyl(aryl), CONH-alkyl, CONH-alkyl;

R² is hydrogen;

R³ is oxo, hydroxy, alkoxy or NOH;

R⁴ is hydrogen or alkyl;

R⁵ is alkyl(heterocyclo) wherein a hetero atom of the heterocycle is linked to alkyl and alkyl has at least 2 carbons in the chain or R⁵ is alkyl(substituted amino) where alkyl has at least 2 compounds in the chain; and

n is an integer of 0 to 2

with the proviso that

(1) where R³ is oxo, and R¹ is phenylalkyloxy, then R⁵ is alkyl(heterocyclo), or

(2) where R³ is hydroxy, R¹ is phenylalkyloxy, R⁵ is alkyl(heterocyclo) other than ##STR268##

3. A compound as recited in claim 2 wherein R¹ is O-alkyl(aryl);

R² is hydrogen;

R³ is oxo, hydroxy, alkoxy or NOH;

R⁴ is hydrogen or alkyl; and

n is an integer of 0 to 2.

5. The compound as defined in claim 2 wherein R⁵ is heterocycloalkyl wherein heterocyclo is substituted with alkyl, aryl, alkylthio, alkoxy, halo, nitro, keto cyano, hydroxy, azo, oxo, thiazo, amino, substituted amino, carboxylic acid, or carboxylic ester, or alkoxy further substituted with a carboxylic acid or a 5- to 8-membered ring optionally containing 1 to 4 heteroatoms selected from oxygen, nitrogen and sulfur, optionally substituted with alkyl or halogen.

6. The compound as defined in claim 2 wherein R⁵ is piperidinylalkyl.

7. The compound as defined in claim 2 wherein R⁵ is 4-phenyl-1-piperidinylalkyl.

8. The compound as defined in claim 2 wherein R⁵ is 4-phenyl-1-piperidinylethyl.

9. The compound as defined in claim 2 wherein R¹ is arylalkyloxy.

10. The compound as defined in claim 2 wherein R¹ is 2-phenylphenylmethoxy, R⁵ is 4-phenyl-1-piperidinylethyl, R² is H, R³ is oxo and n is 1.

11. The compound as defined in claim 2 having the structure ##STR269##

15. The compound as defined in claim 2 wherein R⁵ is 4-phenyl-1-piperidinylethyl.

4. A compound which is:

1,2,3,4-Tetrahydro-6-methoxy-1-oxo-2-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthaleneacetic acid, methyl ester, monohydrochloride;

3,4-Dihydro-6-methoxy-2-[2-oxo-2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

1,2,3,4-Tetrahydro-6-methoxy-2-(2-(4-phenyl-1-piperidinenyl)ethyl]-1(2H)-naphthalenol, monohydrochloride;

cis-6-([1,1'"'"'-Biphenyl]-2-ylmethoxy)-1,2,3,4-tetrahydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenol, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1;

1);

trans-1,2,3,4-Tetrahydro-6-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenol;

trans-1,2,3,4-Tetrahydro-6-phenyl-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenol;

trans-1,2,3,4-Tetrahydro-6-phenoxy-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenol;

trans-1,2,3,4-Tetrahydro-6-(phenylmethoxy)-2-[2-(1-piperidinyl)ethyl]-1-naphthalenol;

trans-1,2,3,4-Tetrahydro-6-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenol, enantiomer A;

trans-1,2,3,4-Tetrahydro-6-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenol, enantiomer B;

3,4-Dihydro-6-methoxy-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, monohydrochloride;

3,4-Dihydro-6-phenoxy-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, monohydrochloride;

3,4-Dihydro-6-phenyl-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, monohydrochloride;

3,4-Dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-6-(4-pyridinylmethoxy)-1-(2H)-naphthalenone, dihydrochloride;

3,4-Dihydro-6-(2-phenylethyl)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

6-[(1,1,'"'"'-Biphenyl]-2-ylmethoxy)-3,4-dihydro-2-[2-(1-piperidinyl)ethyl]-1(2H)-naphthalenone, monohydrochloride;

3,4-Dihydro-6-(2-methylpropoxy)-2-[2-oxo-2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-6-(3-pyridinylmethoxy)-1(2H)-naphthalenone, dihydrochloride;

3,4-Dihydro-6-[(3-methylphenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

6-[(4-Chlorophenyl)methoxy]-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-6-[(4-methylphenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

6-[(2-Chlorophenyl)methoxy]-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

6-[(3-Chlorophenyl)methoxy]-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-6-[[4-(1-methyletyl)phenyl]methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

4-[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]oxy]methyl]benzonitrile;

3,4-Dihydro-5-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, trifluoroacetate (1;

1);

3,4-Dihydro-56-(phenylmethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-6-(phenylmethoxy)-2-[2-(2-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, isomer A;

3,4-Dihydro-6-(phenylmethoxy)-2-[2-(2-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, isomer B;

3,4-Dihydro-6-[(1-phenyl-1H-imidazol-2-yl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-2-[(4-phenyl-1-piperidinyl)ethyl]-6-(2,2,2-trifluoroethoxy)-1(2H)-naphthalenone, monohydrochloride;

3,4-Dihydro-6-[(3-nitrophenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-6-[(2-methoxyphenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-6-[(2-nitrophenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)naphthalenone;

6-([1,1'"'"'-Biphenyl]-4-ylmethoxy)-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

6-([1,1'"'"'-Biphenyl]-2-ylmethoxy)-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-6-ethoxy-1(2H)-naphthalenone;

3,4-Dihydro-6-[(2-methylphenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

2-[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]oxy]methyl]benzonitrile;

4-[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]oxy]methyl]benzoic acid, methyl ester;

3-[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]oxy]methyl]benzonitrile;

3,4-Dihydro-6-[(4-nitrophenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-6-[(4-methylphenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-6-[(3-methoxyphenyl)methoxy]-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-6-propoxy-1(2H)-naphthalenone;

3,4-Dihydro-6-(1-methylethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

3,4-Dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-6-[(2-propenyl)oxy]-1(2H)-naphthalenone;

3,4-Dihydro-6-(1-phenylethoxy)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, monohydrochloride;

6-(1H-Benzimidazol-2-ylmethoxy)-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, dihydrochloride;

6-([1,1'"'"'-Biphenyl]-3-ylmethoxy)-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

6-(Cyclopropylmethoxy)-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

6-([1,1'"'"'-Biphenyl]-2-ylmethoxy)-3,4-dihydro-2-[2-(1-piperidinyl)ethyl]-1(2H)-naphthalenone, monohydrochloride;

2-[2-(2-Ethyl-1-piperidinyl)ethyl]-3,4-dihydro-6-(phenylmethoxy)-1(2H)-naphthalenone;

3,4-Dihydro-2-[2-[(S)-2-(methoxymethyl)-1-pyrrolidinyl]ethyl]-6-(phenylmethoxy)-1(2H)-naphthalenone, monohydrochloride;

1-[2-[1,2,3,4-Tetrahydro-1-oxo-6-(phenylmethoxy)-2-naphthalenyl]ethyl]-L-proline, phenylmethyl ester;

1-[2-[1,2,3,4-Tetrahydro-1-oxo-6-(phenylmethoxy)-2-naphthalenyl]ethyl]-L-prolinamide;

3,4-Dihydro-6-methoxy-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, oxime, monohydrochloride;

3,4-Dihydro-6-methoxy-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, oxime;

3,4-Dihydro-6-methoxy-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone hydrazone;

N-Methyl-2-[3,4-dihydro-6-methoxy-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenylidene]-hydrazinecarboxamide;

(E)-6-([1,1'"'"'-Biphenyl]-2-ylmethoxy)-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, oxime;

(E)-6-([1,1'"'"'-Biphenyl]-2-ylmethoxy)-3,4-dihydro-2-[2-(1-piperidinyl)ethyl]-1(2H)-naphthalenone, oxime;

(E)-6-Ethoxy-3,4-dihydro-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone, oxime;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxylic acid, methyl ester;

5,6,7,8-Tetrahydro-5-oxo-N-phenyl-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-pentyl-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

1-[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]carbonyl]piperidine;

5,6,7,8-Tetrahydro-N-(1H-imidazol-2-yl)ethyl]-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, dihydrochloride;

2-[[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]carbonyl]amino]acetic acid, ethyl ester;

4-[[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]carbonyl]amino]-1-piperidinecarboxylic acid, ethyl ester;

5,6,7,8-Tetrahydro-N-[3-(2-oxo-1-pyrrolidinyl)propyl]-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-([1,1-Biphenyl]2-yl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, monohydrochloride;

5,6,7,8-Tetrahydro-5-oxo-N-methyl-N-phenyl-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-(1-methylethyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-(phenylmethyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-[3,5-Bis(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, monohydrochloride;

5,6,7,8-Tetrahydro-N-(3,3-dimethylbutyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, monohydrochloride;

4-[[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]carbonyl]amino]benzoic acid, methyl ester;

5,6,7,8-Tetrahydro-N-(2-methoxyphenyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, monohydrochloride;

5,6,7,8-Tetrahydro-N-(3-pyridinyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, monohydrochloride;

5,6,7,8-Tetrahydro-N-(3,4-dimethyl-5-isoxazolyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, monohydrochloride;

5,6,7,8-Tetrahydro-N-[2-(1-methylethyl)phenyl]-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, (1;

1.37) hydrochloride;

N-(3-Chlorophenyl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, (1;

2.07) hydrochloride;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-(4-pyridinyl)-2-naphthalenecarboxamide, monohydrochloride;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxylic acid, 1-phenylhydrazide, dihydrochloride;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-(4-pyridinyl)-2-naphthalenecarboxylic acid, 2-phenylhydrazide, hydrochloride;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-methoxy-N-methyl-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-([1,1-Biphenyl]-3-yl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-(1H-pyrrol-1-yl)-2-naphthalenecarboxamide, monohydrochloride;

5,6,7,8-Tetrahydro-5-oxo-N-(2-phenylethyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-(2-phenoxyphenyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, monohydrochloride;

N-(3,5-Dimethoxyhenyl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, monohydrochloride;

N-(3,5-Bis(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalene-carboxamide, monohydrochloride;

N-(1,1-Biphenyl]-2-ylmethyl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, (1;

1.07) hydrochloride;

(3-phenylpropyl)-2-naphthalenecarboxamide 5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-(4-phenylbutyl)-2-naphthalenecarboxamide;

N-[2-Cyclohexen-1-yl)ethyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-[2-(3,4-Dimethoxyphenyl)ethyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-[2,2-Diphenylethyl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-[2,3-Dihydro-1H-inden-2-yl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-[2-(1-naphthalenyl)ethyl]-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, hydrochloride;

5,6,7,8-Tetrahydro-N-[2-(2-naphthalenyl)ethyl]-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-[(2,2-Dimethylcyclopentyl)methyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

trans-5,6,7,8-Tetrahydro-5-oxo-N-(2-phenylcyclopropyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-(1-naphthalenylmethyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-[(S)-2-phenylcyclopropyl)-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-[(R)-2-phenylcyclopropyl)-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-[(R)-1-(hydroxymethyl)-3-methylbutyl]-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalene-carboxamide;

5,6,7,8-Tetrahydro-N-[(S)-1-(hydroxymethyl)-3-methylbutyl]-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalene-carboxamide;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-[2-(2-thienyl)ethyl]-2-naphthalenecarboxamide;

N-[(1-(4-Chlorophenyl)cyclopropyl]methyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalene-carboxamide;

N-[2-(4-Dibenzofuranyl)ethyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-(3-hydroxy-2,3-diphenylpropyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

cis-5,6,7,8-Tetrahydro-5-oxo-N-(2-phenylcyclopropyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-(2,2,3,3,3-pentafluoropropyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-(2-methylbutyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, trifluoroacetate;

5,6,7,8-Tetrahydro-N-(3-methylbutyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, trifluoroacetate;

5,6,7,8-Tetrahydro-N-(1-methylbutyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, trifluoroacetate;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-[(tetrahydro-2-furanyl)methyl]-2-naphthalenecarboxamide, trifluoroacetate;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-(2-phenylpropyl)-2-naphthalenecarboxamide, trifluoroacetate;

5,6,7,8-Tetrahydro-N-(2-hydroxy-2-phenylethyl)-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, trifluoroacetate;

N-[2-(2-Fluorophenyl)ethyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, trifluoroacetate;

N-[2-(4-Fluorophenyl)ethyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-6-naphthalenecarboxamide, trifluoroacetate;

N-[2-(3-Fluorophenyl)ethyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, trifluoroacetate;

N-[2-(4-Chlorophenyl)ethyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-[2-(1H-indol-3-yl)ethyl]-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-(3,3-Diphenylpropyl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-[2-(4-phenoxyphenyl)ethyl]-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

3,4-Dihydro-6-methoxy-2-[3-(4-phenyl-1-piperidinyl)propyl]-1(2H)-naphthalenone, monohydrochloride;

(E)-3,4-Dihydro-6-methoxy-2-[(4-phenyl-1-piperidinyl)propyl]-1(2H)-naphthalenone, oxime;

5,6,7,8-Tetrahydro-5-(hydroxyimino)-N-phenyl-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-(hydroxyimino)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxylic acid, methyl ester;

5,6,7,8-Tetrahydro-5-(hydroxyimino)-N-phenyl-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

N-(3,3-Dimethylbutyl)-5,6,7,8-tetrahydro-5-(hydroxyimino)-6-[2-(4-phenyl)-1-piperidinyl)ethyl]-2-naphthalenecarboxamide;

2-[[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]carbonyl]amino]acetic acid;

1,2,3,4-Tetrahydro-6-(hydroxymethyl)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenol

cis-5,6,7,8-Tetrahydro-5-hydroxy-N-phenyl-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenecarboxamide, trifluoroacetate;

3,4-Dihydro-6-(phenylacetyl)-2-[2-(4-phenyl-1-piperidinyl)ethyl]-1(2H)-naphthalenone;

5,6,7,8-Tetrahydro-5-oxo-N-(phenylmethyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthaleneacetamide;

N-[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]methyl]benzeneacetamide

3,3-Dimethyl-N-[[5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]methyl]butanamide and;

N-[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]methyl]benzeneacetamide;

3,3-Dimethyl-N-[[5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-2-naphthalenyl]butanamide;

N-(3,3-Dimethylbutyl)-5,6,7,8-tetrahydro-6-[2-(4-phenyl-1-piperidinyl)ethyl]-5-oxo-1-naphthalenecarboxamide;

N-[[3,5 Bis(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydro-6-[2-(4-phenyl-1-piperidinyl)ethyl]-5-oxo-1-naphthalene-carboxamide;

5,6,7,8-Tetrahydro-N-(phenylmethyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-5-oxo-1-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-pentyl-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

N-([1,1'"'"'-Biphenyl]-2-yl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

1-[[5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenyl]carbonyl]piperidine, (E)-2-butenedioate (1;

1);

5,6,7,8-Tetrahydro-5-oxo-N-(2-phenylethyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-[(R)-1-phenylethyl]-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-[(S)-1-phenylethyl]-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

N-(3,5-Dimethoxyphenyl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

N-(2,5-Dimethoxyphenyl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

N-([1,1'"'"'-Biphenyl]-2-ylmethyl)-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

N-(3,5-Bis(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

N-([1,1'"'"'-Biphenyl]-3-yl))-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-methyl-5-oxo-N-phenyl-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-N-(2-phenoxyphenyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-N-(3-phenylpropyl)-1-naphthalenecarboxamide;

N-[(2,2-Dimethylcyclopentyl)methyl]-5,6,7,8-tetrahydro-5-oxo-6-[2-(4-phenyl-1-piperidinyl)ethyl]-1-naphthalenecarboxamide;

5,6,7,8-Tetrahydro-N-phenyl-N-(phenylmethyl)-6-[2-(4-phenyl-1-piperidinyl)ethyl]-5-oxo-1-naphthalenecarboxamide.