Alpha, beta-unsaturated sulfoxides for treating proliferative disorders

A compound of Formula IA:

• wherein:
• A1 is aryl or heteroaryl and x is 0, 1, 2, 3, 4 or 5;
• either B1 is aryl and y is 1, 2, 3, 4 or 5, or B1 is heteroaryl and y is 0, 1, 2, 3, 4 or 5;
• provided that x does not exceed the number of substitutable positions of the ring to which each Ra is attached;
• and y does not exceed number of substitutable positions of the ring to which each Rb is attached;
• n is 1;
• R1 is —H, —(C1-C8)hydrocarbyl, —CN, —CO2(C1-C6)alkyl or halo(C1-C6)alkyl;
• the configuration of the substituents on the carbon-carbon double bond is either E- or Z—;
• the configuration of the substituents on the sulfoxide sulfur atom is R—, S— or any mixture of R— and S—;
• each Ra is independently selected from the group consisting of halogen;
• —(C1-C8)hydrocarbyl, —C(═O)R2, —NR22, —NHC(═O)R3, —NHSO2R3, —NHR4, —NHCR2R4C(═O)R6, —C(═O)OR2, —C(═O)NHR2;
• —NO2, —CN, —OR2, —P(═O)(OH)2, dimethylamino(C2-C6 alkoxy), —NHC(═NH)NHR2, —(C1-C6)haloalkyl, —(C1-C6)haloalkoxy and —N═CH—R7;
• each Rb attached to aryl is independently selected from the group consisting of —C(═O)R2, halogen, —NO2, —CN, —OR2, —C(═O)OR2, —NR22, (C1-C6)haloalkyl and (C1-C6)haloalkoxy;
• each Rb attached to heteroaryl is independently selected from the group consisting of —(C1-C8)hydrocarbyl, —C(═O)R2, halogen, —NO2, —CN, —OR2, —C(═O)OR2, —NR22, (C1-C6)haloalkyl and (C1-C6)haloalkoxy;
• each R2 is independently selected from the group consisting of —H and —(C1-C8)hydrocarbyl;
• each R3 is independently selected from the group consisting of —H, —(C1-C8)hydrocarbyl, —O(C1-C8)hydrocarbyl, substituted and unsubstituted aryl, substituted heterocyclyl(C1-C3)alkyl, heteroaryl(C1-C3)alkyl, —(C2-C10)heteroalkyl, —(C1-C6)haloalkyl, —CR2R4NHR5, —N(R2)2, —(C1-C3)alkyleneNH2, —(C1-C3)alkylene-N(CH3)2, —(C1-C3)perfluoroalkylene-N(CH3)2, —(C1-C3)alkylene-N+((C1-C3)alkyl)3, —(C1-C3)alkylene-N+(CH2CH2OH)3, —(C1-C3)alkylene-OR2, —(C1-C4)alkylene-CO2R2, —(C1-C4)alkylene-C(═O)halogen, halo(C1-C3)alkyl-, —(C1-C3)alkylene-C(═O)(C1-C3)alkyl, and —(C1-C4)perfluoroalkylene-CO2R2;
• each R4 is independently selected from the group consisting of —H, —(C1-C6)alkyl, —(CH2)3—NH—C(NH2)(═NH), —CH2C(═O)NH2, —CH2COOH, —CH2SH, —(CH2)2C(═O)—NH2, —(CH2)2COOH, —CH2-(2-imidazolyl), —(CH2)4—NH2, —(CH2)2—S—CH3, phenyl, —CH2-phenyl, —CH2—OH, —CH(OH)—CH3, —CH2-(3-indolyl), and —CH2-(4-hydroxyphenyl);
• each R5 is independently selected from the group consisting of —H and a carboxy terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal amino group of the peptidyl residue is present as a functional group selected from the group consisting of —NH2 and —NHC(═O)(C1-C6)alkyl, —NH(C1-C6)alkyl, —N(C1-C6alkyl)2 and —NHC(═O)O(C1-C7)hydrocarbyl;
• each R6 is independently selected from the group consisting of —OR2 and an N-terminally linked peptidyl residue containing from 1 to 3 amino acids in which the terminal carboxyl group of the peptidyl residue is present as a functional group selected from the group consisting of —CO2R2 and —C(═O)NR22;
• and
• each R7 is independently selected from the group consisting of substituted and unsubstituted aryl and substituted and unsubstituted heteroaryl;
• * indicates that, when R1 is other than —H, the configuration of the substituents on the designated carbon atom is R—, S— or any mixture of R— and S—;
• or a salt of such a compound.