C-15 thiazol-4-yl analogues of (E)-9,10-didehydroepothilone D: synthesis and cytotoxicity

The syntheses and biological evaluation of six epothilone D analogues are reported. These side-chain variants of the (E)-9,10-didehydroepothilone scaffold contain C-15 thiazole appendages that are derived from bromomethyl ketone intermediates. Although each of these analogues is less cytotoxic than the parent (E)-9,10-didehydroepothilone D, three maintain IC(50) values in the double-digit nanomolar range against both susceptible and resistant cell lines.