Sigma receptor ligands and the use thereof

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound of the formula:

• ##STR284## wherein:
• R is hydrogen or C.sub.1 -C.sub.6 alkyl;
• T is aryl, heteroaryl, substituted aryl, substituted heteroaryl, or cycloalkyl, wherein said substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, Cl-C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, Cl-C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkylcarbamoyl, nitro, C.sub.2 -C.sub.15 dialkylsulfamoyl, and an ortho methylenedioxy group;
• R.sup.1 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluoro, bromo, chloro, iodo and =0;
• or
• R and R.sup.1 together form a morpholino, piperazinyl or piperidinyl ring;
• n is 0-5;
• X is --(CH.sub.2).sub.q --, wherein q is 1-6;
• --(CH.sub.2).sub.r --C.dbd.C--(CH.sub.2).sub.r --, wherein r is 0-3;
• --(CH.sub.2).sub.r --CH.dbd.CH--(CH.sub.2).sub.r --;
• ##STR285## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein each r is independently 0-3 and wherein Y is O or S;
• or
• C.sub.1 -C.sub.6 alkyl (wherein Z is hydrogen);
• Z is hydrogen, cycloalkyl, aryl, an aryl-substituted carboxylic acid group, or aryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkylcarbamoyl, nitro, C.sub.2 -C.sub.15 dialkylsulfamoyl, or an ortho methylene-dioxy group;
• wherein said compound exhibits high binding activity with respect to the sigma receptor.

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraine or depression, which comprises administering to said, human a therapeutically effective amount of a compound of the formula:

• ##STR286## wherein:
• R is hydrogen or C.sub.1 -C.sub.6 alkyl;
• Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl;
• C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkylcarbamoyl, nitro and C.sub.2 -C.sub.15 dialkylsulfamoyl;
• R.sup.1 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluoro, chloro, bromo, iodo and =0;
• or
• R and R.sup.1 together form a morpholino, piperazinyl or piperidinyl ring;
• n is 1-3;
• p is 1-3;
• X is --(CH.sub.2).sub.q --, wherein q is 1-6;
• --(CH.sub.2).sub.r --C.dbd.C--(CH.sub.2).sub.r --;
• --(CH.sub.2).sub.r --CH=CH--(CH.sub.2).sub.r --, ##STR287## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein each r is independently 0-3 and wherein Y is O or S;
• or
• C.sub.1 -C.sub.6 alkyl;
• Z is hydrogen, cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkyl-sulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkylcarbamoyl, nitro, C.sub.2 -C.sub.15 dialkylsulfamoyl or methylenedioxy;
• wherein said compound exhibits a high binding activity with respect to the sigma receptor.

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound of the formula:

• ##STR288## wherein:
• R.sup.4 is hydrogen or an aryl group substituted with a group selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.3 -C.sub.15 dialkylaminoalkyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, C.sub.2 -C.sub.6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl;
• R.sup.5 is hydrogen or hydroxy;
• X is --(CH.sub.2).sub.q --, wherein q is 1-6;
• --(CH.sub.2).sub.r --C.dbd.C--(CH.sub.2).sub.r --,
• --(CH.sub.2).sub.r --CH.dbd.CH--(CH.sub.2).sub.r --;
• ##STR289## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein each r is independently 0-3 and wherein Y is O or S;
• or
• C.sub.1 -C.sub.6 alkyl (wherein Z is hydrogen);
• Z is cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkyl-amino, dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialklcarbamoyl, nitro, C.sub.2 -C.sub.15 dialkylsulfamoyl or methylenedioxy;
• wherein said compound exhibits a high binding activity with respect to the sigma receptors.

A method of treating a human being suffering from a sigma reception associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

• ##STR290## wherein, X is --(CH.sub.2).sub.q --, wherein q is 1-6,
• --(CH.sub.2).sub.r --C.dbd.C--(CH.sub.2).sub.r --;
• --(CH.sub.2).sub.r --CH.dbd.CH--(CH.sub.2).sub.r --;
• ##STR291## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein each r is independently 0-3 and wherein Y is O or S;
• or
• C.sub.1 -C.sub.6 alkyl (wherein Z is hydrogen);
• Z is cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkyl-amino, dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialklcarbamoyl, nitro, C.sub.2 -C.sub.15 dialkylsulfamoyl or methylenedioxy;
• wherein said compound exhibits a high binding activity with respect to the sigma receptors.

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound of the formula:

• ##STR292## wherein a is 1-8;
• b is 1-8;
• R is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialklcarbamoyl, nitro and C.sub.2 -C.sub.15 dialkylsulfamoyl;
• wherein said compound exhibits high binding activity with respect to the sigma receptor.

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound having the Formula:

• ##STR293## wherein a is 1-8;
• b is 1-8;
• R is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkyl-amino, dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialklcarbamoyl, nitro and C.sub.2 -C.sub.15 dialkylsulfamoyl;
• and
• wherein said compound exhibits high binding activity with respect to the sigma receptor.

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

• ##STR294## wherein;
• Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl, wherein the substituent is selected from the group consisting of chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkylcarbamoyl, nitro and C.sub.2 -C.sub.15 dialkylsulfamoyl;
• X is --(CH.sub.2).sub.q --, wherein q is 1-6;
• --(CH.sub.2).sub.r --CH.dbd.C--(CH.sub.2).sub.r --;
• --(CH.sub.2).sub.r --CH.dbd.CH--(CH.sub.2).sub.r --;
• ##STR295## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein each r is independently 0-3 and wherein Y is O or S;
• or
• C.sub.1 -C.sub.6 alkyl;
• Z is hydrogen, cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkylcarbamoyl, nitro, C.sub.2 -C.sub.15 dialkylsulfamoyl or methylenedioxy;
• wherein said compound exhibits high binding activity with respect to the sigma receptor.

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder, psychosis, angina, hypertension, migraine or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

• ##STR296## wherein n is 0-5;
• Cy is C.sub.3 -C.sub.8 cycloalkyl;
• R is hydrogen or C.sub.1 -C.sub.6 alkyl;
• R.sup.1 is independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluoro, chloro, bromo, iodo and =0;
• X is --(CH.sub.2).sub.q --, wherein q is 1-6;
• --(CH.sub.2).sub.r --C.dbd.C--(CH.sub.2).sub.r --, wherein r is 0-3;
• --(CH.sub.2).sub.r --CH.dbd.CH--(CH.sub.2).sub.r --;
• ##STR297## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein each r is independently 0-3 and wherein Y is O or S;
• or
• C.sub.1 -C.sub.6 alkyl (wherein Z is hydrogen);
• and
• Z is hydrogen, cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkylcarbamoyl, nitro, C.sub.2 -C.sub.15 dialkylsulfamoyl or methylenedioxy;
• wherein said compound exhibits high binding activity with respect to the sigma receptor.

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, psychosis, angina, hypertension, migraine drug abuse, gastrointestinal disorder or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

• ##STR298## wherein X.sup.1 is --(CH.sub.2).sub.r --C.dbd.C--(CH.sub.2).sub.r --, wherein each r is 0-3 independently;
• --(CH.sub.2).sub.r --CH.dbd.CH--(CH.sub.2).sub.r --;
• ##STR299## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein Y is O or S;
• or C.sub.1 -C.sub.6 alkyl (wherein Z is hydrogen);
• R.sup.2 is independently selected from the group consisting of hydrogen, chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkyl-amino, dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkicarbamoyl, nitro and C.sub.2 -C.sub.15 dialkylsulfamoyl;
• V is N or CM, wherein M is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluoro, chloro, bromo, trifluoromethyl, hydroxy or one half of a double bond with the neighboring endocyclic carbon;
• X is --(CH.sub.2)q-l wherein q is 1-6;
• --(CH.sub.2).sub.r --C.dbd.C--(CH.sub.2).sub.r --, wherein r is 0-3;
• --(CH.sub.2).sub.r --CH.dbd.CH--(CH.sub.2).sub.r --;
• ##STR300## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein each r is independently 0-3 and wherein Y is O or S;
• or
• C.sub.1 -C.sub.6 alkyl (wherein Z is hydrogen);
• and
• Z is hydrogen, cycloalkyl, aryl or heteroaryl wherein Z may be substituted by chloro, fluoro, bromo, iodo, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 dialkoxymethyl, C.sub.1 -C.sub.6 alkyl, cyano, C.sub.3 -C.sub.15 dialkylaminoalkyl, carboxy, carboxamido, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 haloalkylthio, allyl, aralkyl, C.sub.3 -C.sub.6 cycloalkyl, aroyl, aralkoxy, C.sub.2 -C.sub.6 carboxylic acyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, C.sub.3 -C.sub.6 heterocycloalkyl, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfonyl, C.sub.1 -C.sub.6 haloalkylsulfonyl, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 haloalkylsulfinyl, arylthio, C.sub.1 -C.sub.6 haloalkoxy, amino, C.sub.1 -C.sub.6 alkylamino, C.sub.2 -C.sub.15 dialkylamino, hydroxy, carbamoyl, C.sub.1 -C.sub.6 N-alkylcarbamoyl, C.sub.2 -C.sub.15 N,N-dialkylcarbamoyl, nitro and C.sub.2 -C.sub.15 dialkylsulfamoyl;
• wherein said compound exhibits high binding activity with respect to the sigma receptor.

A method of treating a human being suffering from a sigma receptor associated central nervous system disorder, drug abuse, gastrointestinal disorder psychosis, angina, hypertension, migraines or depression, which comprises administering to said human a therapeutically effective amount of a compound having the formula:

• ##STR301## wherein R.sup.5 and R.sup.6 are independently a C.sub.1-8 alkyl group;
• R.sup.7 is hydrogen or a C.sub.1-8 alkyl group substituted by an arylacetoxy or arylcarboxy group;
• and
• X is --(CH.sub.2).sub.q --, wherein q is 1-6;
• --(CH.sub.2).sub.r --C.dbd.C--(CH.sub.2).sub.r --, wherein r is 0-3;
• --(CH.sub.2).sub.r --CH.dbd.CH--(CH.sub.2).sub.r --;
• ##STR302## --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.r --, wherein each r is independently 0-3 and wherein Y is O or S;
• or
• C.sub.1 -C.sub.6 alkyl (wherein R.sup.7 is hydrogen);
• wherein said compound exhibits a high binding activity with respect to the sigma receptors.