title: C-15 thiazol-4-yl analogues of (E)-9,10-didehydroepothilone D: synthesis and cytotoxicity.
abstract: 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.
authors.affiliation: Kosan Biosciences, Inc., Hayward, California 94545, USA. hearn@kosan.com
authors.forename: Brian R
authors.initials: BR
authors.lastname: Hearn
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: David C
authors.initials: DC
authors.lastname: Myles
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C442200:9,10-dehydroepothilone D; D000970:Antineoplastic Agents; D034261:Epothilones; D013844:Thiazoles