16-Halogen-epothilone derivatives, method for producing them and their pharmaceutical use

Epothilone derivatives of general formula I,

• in which
• R1a, R1b are, each independently, hydrogen, C1-C10 alkyl, aryl, or C7-C20 aralkyl, or together are a —(CH2)m group with m=2, 3, 4 or 5,
• R2a, R2b are, each independently, hydrogen, C1-C10 alkyl, aryl, or C7-C20 aralkyl or together are a —(CH2)n group with n=2, 3, 4 or 5,
• R3 is hydrogen, C1-C10 alkyl, aryl, or C7-C20 aralkyl,
• G is an oxygen atom or a group —CH2,
• R4a, R4b are, each independently, hydrogen, C1-C10 alkyl, aryl, or C7-C20 aralkyl, or together are a —(CH2)p group with p=2, 3, 4 or 5,
• D—E is a group of
• R5 is hydrogen, C1-C10 alkyl, aryl, C7-C20 aralkyl, CO2H, CO2-alkyl, CH2OH, CH2O-alkyl, CH2O-acyl, CN, CH2NH2, CH2N(alkyl, acyl)1,2, or CH2Hal
• R6, R7 each are a hydrogen atom, or together an additional bond or an oxygen atom,
• R8 is a halogen atom, or a cyano group,
• X is an oxygen atom, two alkoxy groups OR23, C2-C10 alkylene-α,ω-dioxy group, which is straight-chain or branched, H/OR9 or a group CR10R11,
• R23 is a C1-C20 alkyl radical,
• R9 is hydrogen or a protective group,
• R10, R11 are, each independently, hydrogen, a C1-C10 alkyl, aryl, or C7-C20 aralkyl radical or R10 and R11 together with the carbon atom they are attached to form a 5- to 7-membered carbocyclic ring,
• T—Y is a group O—C(═O), O—CH2, CH2C(═O), NR24—C(═O), or NR24—SO2,
• R24 is hydrogen, or C1-C10 alkyl,
• Z is an oxygen atom or H/OR12,
• R12 is hydrogen or a protective group.