Anticancer agents based on regulation of protein prenylation

A method of inhibiting the growth of a cancer cell, the method comprising contacting the cancer cell with a compound of Formula IIA:

• A-Y—(C═O)—CX1X2X3(Formula IIA)
• or a pharmaceutically acceptable salt, prodrug, or ester thereof
• where:
• Y is a heteroatom or heteroatomic group independently selected from the group consisting of O, NH, NA′, and S;
• where,
• when Y is O, A is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkylthio, alkenyl, alkynyl, cycloalkyl, haloalkyl, carbocycloalkyl or optionally substituted carbocycloalkyl, heterocyclo or optionally substituted heterocyclo, heteroaryl or optionally substituted heteroaryl, aryl, aralkyl, (heterocyclo)alkyl, (heteroary)alkyl, carboxyalkyl, amino or substituted amino, amido or substituted amido, and alkanoylamido;
• when Y is S, A is selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxyalkyl, aryloxy, cycloalkoxy, alkylthio, alkenyl, alkynyl, cycloalkyl, haloalkyl, carbocycloalkyl or optionally substituted carbocycloalkyl, heterocyclo or optionally substituted heterocyclo, heteroaryl or optionally substituted heteroaryl, aryl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, carboxyalkyl, amino or substituted amino, amido or substituted amido, and alkanoylamido;
• and,
• when Y is NH or NA′, A and A′ are independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxyalkyl, aryloxy, cycloalkoxy, alkylthio, alkenyl, alkynyl, cycloalkyl, haloalkyl, alkanoyl, aroyl, aminocarbonyl, aminoalkanoyl or optionally substituted aminoalkanoyl, carbocycloalkyl or optionally substituted carbocycloalkyl, heterocyclo or optionally substituted heterocyclo, heteroaryl or optionally substituted heteroaryl, halo, aryl, aralkyl, (heterocyclo)alkyl, (heterocyclo)alkyl, alkoxycarbonyl, alkylcarbonyloxy, alkoxyalkanoyl, carboxyalkyl, amino or substituted amino, amido or substituted amido, and alkanoylamido, and
• X1, X2, and X3 are independently selected from the group consisting of hydrogen, halogen, organosulfonyloxy, bromobenzenesulfonyloxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, acyloxy, aryloxy, imidazolyl, —O—N═O, —NO2, —OSO331, and —OPO2(OH)−, with the proviso that X1, X2, and X3 are not all hydrogen.

A method of inhibiting the growth of a cancer cell, the method comprising contacting the cancer cell with a compound of Formula IIB:

• A-Y—(C═S)—CX1X2X3(Formula IIB)
• or a pharmaceutically acceptable salt, prodrug, or ester thereof
• where:
• Y is a heteroatom or heteroatomic group independently selected from the group consisting of O, NH, NA′, and S;
• where,
• when Y is O, A is selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, alkylthio, alkenyl, alkynyl, cycloalkyl, haloalkyl, carbocycloalkyl or optionally substituted carbocycloalkyl, heterocyclo or optionally substituted heterocyclo, heteroaryl or optionally substituted heteroaryl, aryl, arlkyl, (heteroaryl)alkyl, (heteroaryl)alkyl, carboxyalkyl, amino or substituted amino, amido or substituted amido, and alkanoylamido;
• when Y is S, A is selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxyalkyl, aryloxy, cycloalkoxy, alkylthio, alkenyl, alkynyl, cycloalkyl, haloalkyl, carbocycloalkyl or optionally substituted carbocycloalkyl, heterocyclo or optionally substituted heterocyclo, heteroaryl or optionally substituted heteroaryl, aryl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, carboxyalkyl, amino or substituted amino, amido or substituted amido, and alkanoylamido;
• and,
• when Y is NH or NA′, A and A′ are independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxyalkyl, aryloxy, cycloalkoxy, alkylthio, alkenyl, alkynyl, cycloalkyl, haloalkyl, alkanoyl, aroyl, aminocarbonyl, aminoalkanoyl or optionally substituted aminoalkanoyl, carbocycloalkyl or optionally substituted carbocycloalkyl, heterocyclo or optionally substituted heterocyclo, heteroaryl or optionally substituted heteroaryl, halo, aryl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, alkoxycarbonyl, alkylcarbonyloxy, alkoxyalkanoyl, carboxyalkyl, amino or substituted amino, amido or substituted amido, and alkanoylamido, and
• X1, X2, and X3 are independently selected from the group consisting of hydrogen, halogen, organosulfonyloxy, bromobenzenesulfonyloxy, methanesulfonyloxy, trifluoromethanesulfonyloxy, acyloxy, aryloxy, imidazolyl, —O—N═O, —NO2, —OSO3−, and —OPO2 (OH)−, with the proviso that X1, X2, and X3 are not all hydrogen.