Cat-1 inhibitors, pharmaceutical compositions and methods of use

A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula ##STR43## wherein R.sub.1 is hydroxy;

• R.sub.2 and R.sub.2 ', independently, are hydrogen, alkyl, aryl, alkoxy, hydroxy, halogen, alkanoxyl, aroyl or nitro;
• A is a bond, ##STR44## wherein R.sub.7 is hydrogen, lower alkyl or acyl and R.sub.8 and R.sub.9 are, independently, hydrogen or lower alkyl;
• B is a bond;
• ##STR45## wherein m is an integer from 1 to 4 and R.sub.7, R.sub.8, R.sub.9 are as described above and R.sub.10 is hydrogen;
• n is an integer from 1 to 6, with the proviso that when A and B are, independently, a bond, ##STR46## then n is an integer from 2 to 6;
• Z is --S--, --CR.sub.2 .dbd.CR.sub.2 --;
• X and Y taken together are O.dbd., or when one of X or Y is amino, the other is hydrogen;
• Q is phenyl, cyclohexyl, cyclooctyl, pyridinyl, adamantyl, 1,1'-biphenyl, anthracenyl, phenanthrenyl, naphthalenyl, 5,6,7,8-tetrahydro-1-naphthalenyl, 5,6,7,8-tetrahydro-2-naphthalenyl, 1,2,3,4-tetrahydro-1-naphthalenyl, 1,2,3,4-tetrahydro-2-naphthalenyl, quinolyl, isoquinolyl, which radical can be substituted by one or more of the following groups, lower alkyl, alkoxy, acyloxy, halogen, acyloxyalkyl, alkoxyalkyl, aryloxyalkoxy, hydroxy, hydroxyalkyl, hydroxyalkoxy, phenyl, trihaloalkyl, sulfamoyl, carboxycarbonyl or alkoxyalyl;
• or
• when a basic or acidic group is present, its pharmaceutically acceptable salt, and, when appropriate, its enantiomer, racemate, diastereomer or mixture thereof or geometric isomer or mixture thereof, or a pharmaceutically acceptable salt thereof.

A method of inhibiting carnitine acryltransferase in a host which comprises administering to such a host an effective amount of a compound of the formula ##STR53## wherein R.sub.1 is hydroxy, R.sub.2 and R.sub.2 ', independently, are is hydrogen, lower alkyl, aryl, aryl-lower alkyl, lower alkoxy, hydroxy, amino, lower alkylamino, di-lower alkylamino, cyano, halogen, mercapto, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trihalo-lower alkyl, acyl or nitro;

• A is a bond, ##STR54## `wherein R.sub.7 is hydrogen, lower alkyl or acyl and R.sub.8 and R.sub.9 are, independently, hydrogen or lower alkyl;
• n is an integer from 0 to 10;
• B is a bond, ##STR55## wherein m is an integer from 1 to 4 and R.sub.7, R.sub.8, R.sub.9 are as described above and R.sub.10 is hydrogen or lower alkyl;
• Z is ##STR56## wherein R.sub.11 is hydrogen or lower alkyl;
• X and Y taken together are O.dbd., S.dbd., or when one of X or Y is amino, lower-alkylamino or di-lower alkylamino, the other is hydrogen, lower alkyl or aryl-lower alkyl;
• Q is a cycloalkyl, aryl or heterocyclic radical;
• provided that, when A is oxygen (O) and B is a bond, sulfur (S) or oxygen (O), then n is 2-10;
• or, when a basic or acidic group is present, its pharmaceutically acceptable salt, and when appropriate, its enantiomer, racemate, diastereomer or mixture thereof or geometric isomer or mixture thereof, or a pharmaceutically acceptable salt thereof.