法尼基转移酶新型抑制剂的固相合成

Solid-phase synthesis of novel inhibitors of farnesyl transferase.

作者信息

Barber A M, Hardcastle I R, Rowlands M G, Nutley B P, Marriott J H, Jarman M

机构信息

Cancer Research Campaign Laboratory, CRC Centre for Cancer Therapeutics at the Institute of Cancer Research, Sutton, Surrey, UK.

出版信息

Bioorg Med Chem Lett. 1999 Feb 22;9(4):623-6. doi: 10.1016/s0960-894x(99)00043-8.

DOI:10.1016/s0960-894x(99)00043-8

PMID:10098677

Abstract

A novel diphosphate mimic, the 2,3,6-trifluoro-5-hydroxy-4-nitrophenoxy group (1), has been employed as the template in the solid-phase synthesis of novel farnesyl transferase inhibitors using the Mitsunobu reaction. The most potent inhibitor (farnesyloxy-5-hydroxy-2,3,6-trifluoro-4-nitrobenzene) displayed an IC50 of 6.3 microM versus farnesyl transferase.

摘要

一种新型二磷酸类似物，即2,3,6-三氟-5-羟基-4-硝基苯氧基（1），已被用作模板，通过光延反应进行新型法尼基转移酶抑制剂的固相合成。最有效的抑制剂（法尼基氧基-5-羟基-2,3,6-三氟-4-硝基苯）对法尼基转移酶的IC50为6.3微摩尔。