1-(4-Aryl-cyclohexyl)piperidine derivatives, method of use thereof and pharmaceutical compositions thereof

Claim 1

A chemical compound represented by the formula ##STR36## the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein Ar 1 is a member selected from the group consisting of aryl and 1,3-benzodioxolyl; R is a member selected from the group consisting of hydrogen and lower alkyl; R 1 is a member selected from the group consisting of hydrogen, cyano, carboxyl, lower alkyloxycarbonyl, aryllower alkyloxycarbonyl, aminocarbonyl, mono- and di(lower alkyl)aminocarbonyl, mono- and di(aryllower alkyl)aminocarbonyl, (aryllower alkyl)lower alkylamino-carbonyl, hydroxy, lower alkyloxy, lower alkylcarbonyloxy, formyl, lower alkylcarbonyl, arylcarbonyl, aryllower alkylcarbonyl, lower alkyl, lower alkenyl, lower alkynyl and cyclohexyl; and A has the formula ##STR37## wherein R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, lower alkyl and lower alkyloxy; or A has the formula ##STR38## wherein Ar 2 is aryl, and R 4 is a member selected from the group consisting of hydrogen, lower alkyl, aryllower alkyl, cyanolower alkyl, aminolower alkyl, mono- and di(lower alkyl)aminolower alkyl, mono- and di(aryllower alkyl)amino-lower alkyl, lower alkyl, hydroxy-lower alkyl, mercaptolower alkyl, lower alkyloxylower alkyl, lower alkylthiolower alkyl, aryloxylower alkyl, arylthiolower alkyl, aryllower alkyloxylower alkyl, aryllower alkylthiolower alkyl, and a radical of formula ##STR39## wherein n is 0 or an integer of from 1 to 6 inclusive, Q is O, S or NR 6 , p is 0 or 1, X is O or S, R 5 is hydrogen, lower alkyl, aryl or aryllower alkyl, m is 0 or 1 and Y is O, S or NR 6 , wherein R 6 as used in the definition of Q and Y is hydrogen, lower alkyl, aryl or aryllower alkyl: provided that when Y is O and m and p are each 1 than R 5 is other than hydrogen and provided that when p is 1 than n is other than 0; wherein aryl, whether used alone or as a portion of another term, is a member selected from the group consisting of phenyl, thienyl, pyridinyl, naphthalenyl and substituted phenyl, said substituted phenyl having from 1 to 3- substituents each independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, phenyl lower alkyloxy, trifluoromethyl, nitro, amino and hydroxy.

Claim 15

A method of inhibiting emesis or mental disorders which comprise the systemic administration to warm-blooded animals of an effective antiemetic or psychotropic amount of a compound represented by the formula ##STR46## the pharmaceutically acceptable acid addition salts and the stereo-chemically isomeric forms thereof, wherein Ar 1 is a member selected from the group consisting of aryl and 1,3-benzodioxolyl; R is a member selected from the group consisting of hydrogen and lower alkyl; R 1 is a member selected from the group consisting of hydrogen, cyano, carboxyl, lower alkyloxycarbonyl, aryllower alkyloxycarbonyl, aminocarbonyl, mono- and di(lower alkyl)aminocarbonyl, mono- and di(aryllower alkyl)aminocarbonyl, (aryllower alkyl)lower alkylamino- carbonyl, hydroxy, lower alkyloxy, lower alkylcarbonyloxy, formyl, lower alkylarbonyl, arylcarbonyl, aryllower alkylcarbonyl, lower alkyl, lower alkenyl, lower alkynyl and cyclohexyl; and A has the formula ##STR47## wherein R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, lower alkyl and lower alkyloxy; or A has the formula ##STR48## wherein Ar 2 is aryl, and R 4 is a member selected from the group consisting of hydrogen, lower alkyl, aryllower alkyl, cyanolower alkyl, aminolower alkyl, mono- and di(lower alkyl)aminolower alkyl, mono- and di(aryllower alkyl)-aminololower alkyl, lower alkyl, hydroxylower alkyl, mercaptolower alkyl, lower alkyloxylower alkyl, lower alkylthiolower alkyl, aryloxylower alkyl, arylthiolower alkyl, aryllower alkyloxylower alkyl, aryllower alkylthiolower alkyl, and a radical of formula ##STR49## wherein n is o or an integer of from 1 to 6 inclusive, Q is O, S or NR 6 , p is o or 1, X is O or S, R 5 is hydrogen, lower alkyl, aryl or aryllower alkyl, m is o or 1 and Y is O, S or NR 6 , wherein R 6 as used in the definition of Q and Y is hydrogen, lower alkyl, aryl or aryllower alkyl; provided that when Y is O and m and p are each 1 than R 5 is other than hydrogen and provided that when p is 1 than n is other than o; wherein aryl, whether used alone or as a portion of another term, is a member selected from the group consisting of phenyl, thienyl, pyridinyl, naphthalenyl and substituted phenyl, said substituted phenyl having from 1 to 3 substituents each independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, phenyl lower alkyloxy, trifluoromethyl, nitro, amino and hydroxy.

Claim 16

A method of inhibiting emesis or mental disorders which comprise the systemic administration to warm-blooded animals of an effective antiemetic or psychotropic amount of a compound represented by the formula ##STR46## the pharmaceutically acceptable acid addition salts and the stereo-chemically isomeric forms thereof, wherein Ar 1 is a member selected from the group consisting of aryl and 1,3-benzodioxolyl; R is a member selected from the group consisting of hydrogen and lower alkyl; R 1 is a member selected from the group consisting of hydrogen, cyano, carboxyl, lower alkyloxycarbonyl, aryllower alkyloxycarbonyl, aminocarbonyl, mono- and di(lower alkyl)aminocarbonyl, mono- and di(aryllower alkyl)aminocarbonyl, (aryllower alkyl)lower alkylamino- carbonyl, hydroxy, lower alkyloxy, lower alkylcarbonyloxy, formyl, lower alkylarbonyl, arylcarbonyl, aryllower alkylcarbonyl, lower alkyl, lower alkenyl, lower alkynyl and cyclohexyl; and A has the formula ##STR47## wherein R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, lower alkyl and lower alkyloxy; or A has the formula ##STR48## wherein Ar 2 is aryl, and R 4 is a member selected from the group consisting of hydrogen, lower alkyl, aryllower alkyl, cyanolower alkyl, aminolower alkyl, mono- and di(lower alkyl)aminolower alkyl, mono- and di(aryllower alkyl)-aminololower alkyl, lower alkyl, hydroxylower alkyl, mercaptolower alkyl, lower alkyloxylower alkyl, lower alkylthiolower alkyl, aryloxylower alkyl, arylthiolower alkyl, aryllower alkyloxylower alkyl, aryllower alkylthiolower alkyl, and a radical of formula ##STR49## wherein n is o or an integer of from 1 to 6 inclusive, Q is O, S or NR 6 , p is o or 1, X is O or S, R 5 is hydrogen, lower alkyl, aryl or aryllower alkyl, m is o or 1 and Y is O, S or NR 6 , wherein R 6 as used in the definition of Q and Y is hydrogen, lower alkyl, aryl or aryllower alkyl; provided that when Y is O and m and p are each 1 than R 5 is other than hydrogen and provided that when p is 1 than n is other than o; wherein aryl, whether used alone or as a portion of another term, is a member selected from the group consisting of phenyl, thienyl, pyridinyl, naphthalenyl and substituted phenyl, said substituted phenyl having from 1 to 3 substituents each independently selected from the group consisting of halo, lower alkyl, lower alkyloxy, phenyl lower alkyloxy, trifluoromethyl, nitro, amino and hydroxy.

Claim 18

A method of inhibiting emesis or mental disorders which comprises the systemic administration to warm-blooded animals of an effective antiemetic or psychotropic amount of a compound selected from the group consisting of (B)-8-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-1-(4-fluorophenyl)-α-methyl-4-oxo-1,3,8-triazaspiro[4,5]decane-3-propanenitrile and the pharmaceutically acceptable acid addition salts thereof.

Claim 19

A method of inhibiting emesis or mental disorders which comprises the systemic administration to warm-blooded animals of an effective antiemetic or psychotropic amount of a compound selected from the group consisting of (B)-8-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-1-(4-fluorophenyl)-α-methyl-4-oxo-1,3,8-triazaspiro[4,5]decane-3-propanenitrile and the pharmaceutically acceptable acid addition salts thereof.

Claim 20

A method of inhibiting emesis or mental disorders which comprises the systemic administration to warm-blooded animals of an effective antiemetic or psychotropic amount of a compound selected from the group consisting of (B)-8-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4,5]decane-3-acetamide and the pharmaceutically acceptable acid addition salts thereof.

Claim 21

A method of inhibiting emesis or mental disorders which comprises the systemic administration to warm-blooded animals of an effective antiemetic or psychotropic amount of a compound selected from the group consisting of (B)-8-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4,5]decane-3-acetamide and the pharmaceutically acceptable acid addition salts thereof.