（E）-9,10-二脱氢埃坡霉素D的C-15噻唑-4-基类似物：合成与细胞毒性

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

作者信息

Hearn Brian R, Zhang Dan, Li Yong, Myles David C

机构信息

Kosan Biosciences, Inc., Hayward, California 94545, USA.

出版信息

Org Lett. 2006 Jul 6;8(14):3057-9. doi: 10.1021/ol061087h.

DOI:10.1021/ol061087h

PMID:16805551

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.

摘要

报道了六种埃坡霉素D类似物的合成及生物学评价。这些（E）-9,10-二脱氢埃坡霉素支架的侧链变体含有源自溴甲基酮中间体的C-15噻唑附属物。尽管这些类似物中的每一种的细胞毒性都低于母体（E）-9,10-二脱氢埃坡霉素D，但其中三种对敏感和耐药细胞系的半数抑制浓度（IC50）值保持在两位数纳摩尔范围内。