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US 5,296,479 AGranted
Treatment of psychosis using 1-cycloalkylpiperidines
AssigneeThe Du Pont Merck Pharmaceutical Company
InventorsGary A. Cain, Paul J. Gilligan, Sang W. Tam
Life of this patent
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Abstract
There are provided cycloalkyl piperidine compounds which are useful in the treatment of physiological or drug-induced psychosis or dyskinesia in a mammal. These novel compounds are selective sigma receptor antagonists and have a low potential for movement disorder side effects associated with typical antipsychotic agents.
Claims25
A method of treating physiological or drug induced psychosis or dyskinesia in a mammal comprising administering to the mammal an antipsychotic or antidyskinetic effective amount of a compound of having the formula:
- ##STR38## or a pharmaceutically acceptable salt thereof, wherein:
- m is 0 to 3;
- n is 0 to 3;
- provided m and n are not both O;
- p is 0 to 3;
- X is O, S, SO, SO.sub.2, NR.sup.6 or CO;
- R.sup.1 R.sup.3, and R.sup.7 independently are H, alkyl of 1 to 5 carbon atoms, halogen, NR.sup.10 R.sup.11, OH, CO.sub.2 H, carboalkoxy of 2 to 6 carbon atoms, CN, Ar.sup.1, alkoxy of 1 to 5 carbon atoms or alkylthio of 1 to 5 carbon atoms;
- R.sup.2, R.sup.4 and R.sup.8 independently are H, alkyl of 1 to 5 carbon atoms, carboalkoxy of 2 to 6 carbon atoms, CN, alkoxy of 1 to 5 carbon atoms or Ar.sup.1 ;
- provided that R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are not alkoxy of 1 to 5 carbon atoms, alkylthio of 1 to 5 carbon atoms, NR.sup.10 R.sup.11 or OH when X is O, S, SO, SO.sub.2 or NR.sup.6 ;
- R.sup.5 is H, alkyl, halogen, OH or alkenyl;
- R.sup.6 is H, alkyl of 1 to 5 carbon atoms or Ar.sup.1 ;
- Ar and Ar.sup.1 independently are naphthyl, pyridyl, pyrimidyl, indolyl, quinolinyl, isoquinolinyl, or phenyl optionally substituted with alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms and 1 to 7 halogen atoms, SH, S(O).sub.t alkyl of 1 to 3 carbon atoms, where t is 1, 2 or 3, dialkylamino of 2 to 6 carbon atoms, halogen, OH, alkylamino of 1 to 3 carbon atoms, NH.sub.2, CN, NO.sub.2, SO.sub.3 H, tetrazole, CO.sub.2 H, carboalkoxy of 2 to 6 carbon atoms, CONH.sub.2, SO.sub.2 NH.sub.2, COR.sup.9, CONR.sup.12 R.sup.13, SO.sub.2 NR.sup.12 R.sup.13, Ar.sup.2, OAr.sup.2 or SAr.sup.2 ;
- Ar.sup.2 is naphthyl or phenyl optionally substituted with alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms and 1 to 7 halogen atoms, alkoxy of 1 to 3 carbon atoms, halogen or alkylthio of 1 to 3 carbon atoms;
- R.sup.9, R.sup.10, R.sup.11, R.sup.12 and R.sup.13 independently are H, alkyl of 1 to 5 carbon atoms or phenyl or R.sup.10 and R.sup.11 taken together are an alkylene chain of 3 to 6 carbon atoms or R.sup.12 and R.sup.13 taken together are an alkylene chain of 3 to 6 carbon atoms;
- and
- a or b is a double bond or a single bond, provided that both are not double bonds.
13 more elements
A method of treating physiological or drug induced psychosis or dyskinesia in a mammal by inhibition of the sigma receptor comprising administering to the mammal an antipsychotic or antidyskinetic effective amount of a compound of having the formula:
- ##STR39## or a pharmaceutically acceptable salt thereof, wherein:
- m is 0 to 3;
- n is 0 to 3;
- provided m and n are not both O;
- p is 0 to 3;
- X is O, S, SO, SO.sub.2, NR.sup.6. CR.sup.7 R.sup.8, CO, or CHOH;
- R.sup.1 R.sup.3, and R.sup.7 independently are H, alkyl of 1 to 5 carbon atoms, halogen, NR.sup.10 R.sup.11, OH, CO.sub.2 H, carboalkoxy of 2 to 6 carbon atoms, CN, Ar.sup.1, alkoxy of 1 to 5 carbon atoms or alkylthio of 1 to 5 carbon atoms;
- R.sup.2, R.sup.4 and R.sup.8 independently are H, alkyl of 1 to 5 carbon atoms, carboalkoxy of 2 to 6 carbon atoms, CN, alkoxy of 1 to 5 carbon atoms or Ar.sup.1 ;
- provided that R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are not alkoxy of 1 to 5 carbon atoms, alkylthio of 1 to 5 carbon atoms, NR.sup.10 R.sup.11 or OH when X is O, S, SO, SO.sub.2 or NR.sup.6 ;
- R.sup.5 is H, alkyl, halogen, OH or alkenyl;
- R.sup.6 is H, alkyl of 1 to 5 carbon atoms or Ar.sup.1 ;
- Ar and Ar.sup.1 independently are naphthyl, pyridyl, pyrimidyl, indolyl, quinolinyl, isoquinolinyl, or phenyl optionally substituted with alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms and 1 to 7 halogen atoms, SH, S(O).sub.t alkyl of 1 to 3 carbon atoms, where t is 1, 2 or 3, dialkylamino of 2 to 6 carbon atoms, halogen, OH, alkylamino of 1 to 3 carbon atoms, NH.sub.2, CN, NO.sub.2, SO.sub.3 H, tetrazole, CO.sub.2 H, carboalkoxy of 2 to 6 carbon atoms, CONH.sub.2, SO.sub.2 NH.sub.2, COR.sup.9, CONR.sup.12 R.sup.13, SO.sub.2 NR.sup.12 R.sup.13, Ar.sup.2, OAr.sup.2 or SAr.sup.2 ;
- Ar.sup.2 is naphthyl or phenyl optionally substituted with alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms and 1 to 7 halogen atoms, alkoxy of 1 to 3 carbon atoms, halogen or alkylthio of 1 to 3 carbon atoms;
- R.sup.9, R.sup.10, R.sup.11, R.sup.12 and R.sup.13 independently are H, alkyl of 1 to 5 carbon atoms or phenyl or R.sup.10 and R.sup.11 taken together are an alkylene chain of 3 to 6 carbon atoms or R.sup.12 and R.sup.13 taken together are an alkylene chain of 3 to 6 carbon atoms;
- and
- a or b is a double bond or a single bond, provided that both are not double bonds.
13 more elements
Dependencies are inferred from the claim text.