4-Benzyl piperidine alkylsulfoxide heterocycles and their use as subtype-selective NMDA receptor antagonists
AssigneeWarner-Lambert Company
InventorsJonathan L. Wright, Suzanne Ross Kesten, Ravindra B. Upasani, Nancy C. Lan
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Abstract
Novel 4-Benzyl piperidine alkylsulfoxide heterocycles are disclosed and their use as subtype selective NMDA receptor antagonists, particularly for the treatment of Parkinson's disease, most preferably in combination with L-DOPA.
Claims28
A compound represented by the formula
- or stereoisomers or a pharmaceutically acceptable salt thereof, wherein R and R′ are independently selected from the group consisting of hydrogen, hydroxy, alkyl, halogen, nitro, cyano, carboxaldehyde, aldehyde amine, lower alkoxy carbonylmethyl, hydroxy lower alkyl, amino carbonylmethyl, hydrazinocarbonylmethyl, acetamido, aryl, aralkyl, amino, a halogenated alkyl group, a lower alkyl amino group or a lower alkoxy group;
- R″ and R′″ are independently selected from the group consisting of hydrogen, hydroxy, alkyl, halogen, amino, a halogenated alkyl group, a lower alkyl amino group or a lower alkoxy group;
- X is hydrogen or hydroxy;
- Z is —CH2— or
- n is 2 to 4;
- and
- Y is O, NH or S.
An enantiomer of 6-[2-[4-(4-Fluoro-benzyl)-piperidin-1-yl]-ethanesulfinyl]-3H-benzoorazol-2-one or a pharmaceutically acceptable salt thereof, wherein said enantiomer is present in at least 50% enantiomeric excess with respect to the other enantiomer.
A pharmaceutical composition comprising (+)-6-{2-4-(4-fluorobenzyl)piperidin-1-yl]ethanesulfinyl}-3H-benzooxazol-2-one or a pharmaceutically acceptable salt thereof, substantially free of (−)-6-{2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanesulfinyl}-3H-benzooxazol-2-one, and a pharmaceutically acceptable carrier or diluent.
A method for treating disorders responsive to the selective blockade of N-methyl-D-aspartate receptor subtypes in an animal suffering thereof which comprises administering in unit dosage form at least one compound represented by the formula
- or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of hydrogen, hydroxy, alkyl, halogen, nitro, cyano, carboxaldehyde, aldehyde amine, lower alkoxy carbonylmethyl, hydroxy lower alkyl, amino carbonylmethyl, hydrazinocarbonylmethyl, acetamido, aryl, aralkyl, amino, a halogenated alkyl group, a lower alkyl amino group or a lower alkoxy group;
- R″ and R′″ are independently selected from the group consisting of hydrogen, hydroxy, alkyl, halogen, amino, a halogenated alkyl group, a lower alkyl amino group or a lower alkoxy group;
- X is hydrogen or hydroxy;
- Z is —CH2— or
- n is 2 to 4;
- and
- Y is O, NH or S.
A method for treating disorders responsive to the selective blockade of N-methyl-D-asparate receptor subtypes in an animal suffering thereof which comprises administering in unit dosage form (+)-6-{2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanesulfinyl}-3H-benzooxazol-2-one or a pharmaceutically acceptable salt thereof, substantially free of (−)-6-{2-[4-(4-fluorobenzyl)piperidin-1-yl)ethanesultinyl}-3H-benzooxazol-2-one.
Dependencies are inferred from the claim text.