Li L, Thomas S A, Klein L L, Yeung C M, Maring C J, Grampovnik D J, Lartey P A, Plattner J J
Anti-Infective Research Division, Abbott Laboratories, Abbott Park, Illinois 60064-3500.
J Med Chem. 1994 Aug 19;37(17):2655-63. doi: 10.1021/jm00043a005.
Taxol (1) is considered a most exciting new drug in cancer chemotherapy. The promising antitumor activity of 9(R)-dihydrotaxol (3) encouraged us to further explore the structure-activity relationship of this new member of the taxane family. Studies indicated that the C-13 side chain of taxol is indispensable for antitumor activity and that the natural substitution pattern of a 2'(R)-hydroxy and a 3'(S)-acylamino group might be optimal. However, relatively little is known about the effects of the 3'-phenyl ring on activity. The synthesis and biological evaluation of analogs of 3 modified at the C-3' position are described. This study revealed that the 3'-phenyl ring was not required for activity and identified several compounds which had equal or greater in vitro and in vivo activity than taxol.
紫杉醇（1）被认为是癌症化疗中一种极其令人兴奋的新药。9（R）-二氢紫杉醇（3）有前景的抗肿瘤活性促使我们进一步探索紫杉烷家族这一新成员的构效关系。研究表明，紫杉醇的C-13侧链对于抗肿瘤活性是不可或缺的，并且2'（R）-羟基和3'（S）-酰氨基基团的天然取代模式可能是最佳的。然而，关于3'-苯环对活性的影响相对了解较少。本文描述了在C-3'位置修饰的3的类似物的合成及生物学评价。该研究表明，活性并不需要3'-苯环，并鉴定出了几种在体外和体内活性与紫杉醇相当或更高的化合物。
