Substituted phenoxy-and phenylthio-derivatives for treating proliferative disorders

A compound according to Formula I:

• wherein:
• A is —S— or —O—;
• R1 is selected from the group consisting of halo(C1-C6)alkyl, —C(═O)Rw, —S(═O)Rw, —SO2Rw, —((C1-C6)hydrocarbylene)Rz, —P(═O)(ORv)2, —C(Ra)(Rv)—C(═O)—Rn, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, —Si[(C1-C6)alkyl]3, and —CH2CH2Si[(C1-C6)alkyl]3;
• each Rv is independently selected from the group consisting of —H and —(C1-C7)hydrocarbyl;
• Rw is selected from the group consisting of NRv2, —ORv, halo(C1-C3)alkyl, —NRvCRvRa—C(═O)—Rn, —CRvRa—N(Rv)—Rc, substituted and unsubstituted aryl, substituted and unsubstituted aryl(C1-C3)alkyl, substituted and unsubstituted heteroaryl, substituted and unsubstituted heteroaryl(C1-C3)alkyl, substituted and unsubstituted heterocyclyl, substituted and unsubstituted heterocyclyl(C1-C3)alkyl, —((C1-C3)alkylene)P(═O)(ORv)2, —(C1-C3)perfluoroalkylene-N(CH3)2, —(C1-C3)alkylene-N((C1-C3)alkyl)2, —(C1-C3)alkylene-N+((C1-C3)alkyl)3, —(C1-C3)alkylene-N+(CH2CH2OH)3, —((C1-C4)alkylene)-C(═O)-halogen, —(C1-C4)perfluoroalkylene-CO2Rv, —((C1-C3)alkylene)C(═O)ORv, and —((C1-C3)alkylene)OC(═O)—((C1-C3)alkylene)C(═O)Ry;
• Ry is selected from the group consisting of —ORv, —NRv2 and —(C1-C6)alkyl;
• Rz is selected from the group consisting of —C(═O)Ry, —NRvCRvRa—C(═O)—Rn, —ORv, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted heterocyclyl(C1-C3)alkyl, and —C(═O)(C1-C3)alkyl;
• each Ra is independently selected from the group consisting of —H, —(C1-C6)alkyl, —(C1-C6)heteroalkyl, —(CH2)3—NH—C(NH2)(═NH), —CH2C(═O)NH2, —CH2COOH, —(CH2)2COOH, substituted and unsubstituted aryl, substituted and unsubstituted aryl(C1-C3)alkyl, substituted and unsubstituted heterocyclyl, and substituted and unsubstituted heterocyclyl(C1-C3)alkyl;
• each Rn is independently selected from the group consisting of —ORv, —NRv2, 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 —CO2Rv and —C(═O)NRv2;
• each Rc 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, —NHC(═O)(C1-C6)alkyl, —NH(C1-C6)alkyl, —NH((C1-C6)alkyl)2 and —NHC(═O)O(C1-C7)hydrocarbyl;
• Q is aryl or heteroaryl;
• each R2 and R3 is independently selected from the group consisting of halogen, —(C1-C7)hydrocarbyl, —C(═O)Rv, —NRv2, —NHC(═O)Rv, —NHSO2Rv, —NHRa, —NHCRvRaC(═O)Rn, —NHSO2Rv, —C(═O)ORv, —C(═O)NHRv, —NO2, —CN, —ORv, —P(═O)(ORv)2, —C(═NH)NH2, dimethylamino(C2-C6)alkoxy, —NHC(═NRv)NHRv, —(C1-C6)haloalkyl, and —(C1-C6)haloalkoxy;
• the two Rv groups on —P(═O)(ORv)2 and —NRv2 may optionally form a five- or six-membered heterocyclic ring, which may further optionally be fused to an aryl or carbocyclic ring;
• a is 0, 1, 2 or 3;
• b is 0, 1, 2 or 3;
• the configuration of the substituents on the exocyclic carbon-carbon double bond is either E- or Z-;
• X is —C*H(Rx)Y—;
• Y is —S(═O)— or —SO2—;
• Rx is selected from the group consisting of —H, —(C1-C6)alkyl, and —C(═O)(C1-C6)alkyl;
• and
• * indicates that, when Rx 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;
• provided that:
• when A is —O—:
• R1 is other than halo(C1-C6)alkyl;
• and
• RZ is other than unsubstituted aryl.