Compounds and methods for inducing apoptosis in proliferating cells

A method of inducing apoptosis in rapidly proliferating cells, said method comprising introducing a pharmacologically effective amount of the compound of formula I:

• wherein
• R1 is carboxyamide;
• R2 is selected from the group consisting of alkyl and haloalkyl;
• and
• Ar is an aryl radical selected from phenyl, biphenyl, naphthyl, anthryl, phenanthrenyl, and fluorenyl;
• and wherein Ar is optionally substituted with one or more radicals selected from the group consisting of halo, azido, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 azidoalkyl, aryl, alkylaryl, haloaryl, haloalkylaryl, and combinations thereof;
• or a pharmaceutically-acceptable salt thereof, to the rapidly proliferating cells.

A method of treating, inhibiting, or delaying the onset of cancer in a subject in need of treatment, the method comprising administering a therapeutically effective amount of a compound having formula I:

• wherein
• R1 is carboxyamide;
• R2 is selected from the group consisting of alkyl and haloalkyl;
• and
• Ar is selected from the group consisting of 2-naphthyl, 4-biphenyl, 9-anthryl, 2-fluorenyl, 4-azidophenyl, 4-azidomethylphenyl, 4-(2-azidoethyl)phenyl, 4-(3-azidopropyl)phenyl, 4-(4-azidobutyl)phenyl, 4-(4-azidophenyl)phenyl, 4-(4-azidomethylphenyl)phenyl, 4-methylphenyl, 4-ethylphenyl, 4-propylphenyl, 4-butylphenyl, 4-(2-bromoethyl)phenyl 4-(3-bromopropyl)phenyl, 4-(4-bromobutyl)phenyl, 4-(trifluoromethyl)phenyl, 4-(4-bromomethylphenyl)phenyl, 4-(4-methylphenyl)phenyl, 4-(4-butylphenyl)phenyl, 4-(4-tert-butylphenyl)phenyl, 2-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 4-(4-chlorophenyl)phenyl, 4-(3,5-dichlorophenyl)phenyl, 4-(2,3-dichlorophenyl)phenyl, 4-(3,5-dimethylphenyl)phenyl, 4-(2,4,5-trichlorophenyl)phenyl, 4-(4-trifluoromethylphenyl)phenyl, 2-phenanthrenyl, 3-indolyl, 2-pyrrolyl, 4-(benzyl)phenyl;
• or a pharmaceutically-acceptable salt thereof.

A method of inducing apoptosis in rapidly proliferating cells, the method comprising introducing a therapeutically effective amount of the compound of formula II:

• wherein
• R3 is selected from the group consisting of carboxyamide and sulfonamide;
• R4 is selected from alkyl and haloalkyl;
• and
• Ar′ is selected from the group consisting of 4-azidophenyl, 4-(2-azidoethyl)phenyl, 4-(3-azidopropyl)phenyl, 4-(4-azidobutyl)phenyl, 4-(4-azidophenyl)phenyl, 4-(4-azidomethylphenyl)phenyl, 2,5-dimethylphenyl, 4-propylphenyl, 4-bromomethylphenyl, 4-(2-bromoethyl)phenyl, 4-(3-bromopropyl)phenyl, 4-(4-bromobutyl)phenyl, 4-(4-bromomethylphenyl)phenyl, 4-(4-tert-butylphenyl)phenyl, 9-anthryl, 4-(4-butylphenyl)phenyl, 4-(4-methylphenyl)phenyl, 4-(4-chlorophenyl)phenyl, 4-(3,5-dichlorophenyl)phenyl, 4-(2,3-dichlorophenyl)phenyl, 4-(3,5-dimethylphenyl)phenyl, 4-(2,4,5-trichlorophenyl)phenyl, 4-(4-trifluoromethylphenyl)phenyl, 2-phenanthrenyl, 3-indolyl, 2-pyrrolyl, 4-(benzyl)phenyl, and 2-fluorenyl;
• or a pharmaceutically-acceptable salt thereof, to the rapidly proliferating cells.

A method for treating, inhibiting, or delaying the onset of a cancer in a subject in need of such treatment, wherein the cancer is selected from the group consisting of leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, bladder cancer, lymphoma, and breast cancer;

• the method comprising administering a therapeutically effective amount of the compound of formula II:
• wherein
• R3 is selected from the group consisting of carboxyamide and sulfonamide;
• R4 is selected from alkyl and haloalkyl;
• and
• Ar′ is selected from the group consisting of 4-azidophenyl, 4-(2-azidoethyl)phenyl, 4-(3-azidopropyl)phenyl, 4-(4-azidobutyl)phenyl, 4-(4-azidophenyl)phenyl, 4-(4-azidomethylphenyl)phenyl, 2,5-dimethylphenyl, 4-propylphenyl, 4-bromomethylphenyl, 4-(2-bromoethyl)phenyl, 4-(3-bromopropyl)phenyl, 4-(4-bromobutyl)phenyl, 4-(4-bromomethylphenyl)phenyl, 4-(4-tert-butylphenyl)phenyl, 9-anthryl, 4-(4-butylphenyl)phenyl, 4-(4-methylphenyl)phenyl, 4-(4-chlorophenyl)phenyl, 4-(3,5-dichlorophenyl)phenyl, 4-(2,3-dichlorophenyl)phenyl, 4-(3,5-dimethylphenyl)phenyl, 4-(2,4,5-trichlorophenyl)phenyl, 4-(4-trifluoromethylphenyl)phenyl, 2-phenanthrenyl, 3-indolyl, 2-pyrrolyl, 4-(benzyl)phenyl, and 2-fluorenyl;
• or a pharmaceutically-acceptable salt thereof, to the subject in need of such treatment.