7,8-二取代苯并内酰胺-V8的合成及其与蛋白激酶C的结合

Synthesis of 7,8-disubstituted benzolactam-V8 and its binding to protein kinase C.

作者信息

Ma D, Zhang T, Wang G, Kozikowski A P, Lewin N E, Blumberg P M

机构信息

State Key Laboratory of Bio-organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.

出版信息

Bioorg Med Chem Lett. 2001 Jan 22;11(2):99-101. doi: 10.1016/s0960-894x(00)00609-0.

DOI:10.1016/s0960-894x(00)00609-0

PMID:11206480

Abstract

7-Methoxy-8-decynyl-benzolactam-V8 4 is synthesized using a catalytic asymmetric alkylation reaction as a key step. This compound shows potent activity to three PKC isozymes tested (Ki =45.6, 91.1, and 121.3 nM to PKCalpha, delta, and epsilon, respectively), indicating that introduction of a suitable substituent at the 7-position of 8-decynyl-benzolactam-V8 only slightly reduces the PKC binding affinity.

摘要

7-甲氧基-8-癸炔基-苯并内酰胺-V8 4的合成以催化不对称烷基化反应作为关键步骤。该化合物对所测试的三种蛋白激酶C（PKC）同工酶显示出强效活性（对PKCα、δ和ε的Ki分别为45.6、91.1和121.3 nM），这表明在8-癸炔基-苯并内酰胺-V8的7位引入合适的取代基只会略微降低PKC结合亲和力。