Epothilone derivatives for the treatment of refractory tumors

A method of treating a tumor in a mammal, said tumor having demonstrated resistance to oncology therapy, comprising administering to said mammal an effective amount of a composition comprising a pharmaceutically acceptable carrier and an epothilone compound of formula I:

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• wherein:
• P-Q is a carbon-carbon double bond or an epoxide;
• G is
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• R is selected from the group of H, alkyl, and substituted alkyl;
• R1 is selected from the group consisting of
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• G1 is selected from the group consisting of H, halogen, CN, alkyl and substituted alkyl;
• G2 is selected from the group consisting of H, alkyl, and substituted alkyl;
• G3 is selected from the group consisting of O, S, and NZ1;
• G4 is selected from the group consisting of H, alkyl, substituted alkyl, OZ2, NZ2Z3, Z2C═O, Z4SO2, and optionally substituted glycosyl;
• G5 is selected from the group consisting of halogen, N3, NCS, SH, CN, NC, N(Z1)3+ and heteroaryl;
• G6 is selected from the group consisting of H, alkyl, substituted alkyl, CF3, OZ5, SZ5, and NZ5Z6;
• G7 is CZ7or N;
• G8 is selected from the group consisting of H, halogen, alkyl, substituted alkyl, OZ10, SZ10, and NZ10Z11;
• G9 is selected from the group consisting of O, S, —NH-NH— and —N═N—;
• G10 is N or CZ12;
• G11 is selected from the group consisting of H2N, substituted H2N, alkyl, substituted alkyl, aryl, and substituted aryl;
• each Z1, Z6, Z9, and Z11 is, independently, selected from the group consisting of H, alkyl, substituted alkyl, acyl, and substituted acyl;
• Z2 is selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, and heterocycle;
• each Z3, Z5, Z8, and Z10 is, independently, selected from the group consisting of H, alkyl, substituted alkyl, acyl, substituted acyl, aryl, and substituted aryl;
• Z4 is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, and heterocycle;
• Z7 is selected from the group consisting of H, halogen, alkyl, substituted alkyl, aryl, substituted aryl, OZ8, SZ8, and NZ8Z9;
• and
• Z12 is selected from the group consisting of H, halogen, alkyl, substituted alkyl, aryl, and substituted aryl;
• with the proviso that when R1 is
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• G1, G2, G3 and G4 cannot simultaneously have the following meanings:
• G1 and G2 are H, G4 is O, and G4 is H or Z2C═O wherein Z2 is an alkyl group,
• and pharmaceutically acceptable salts thereof and any hydrates, solvates or geometric, optical and stereoisomers thereof.