Analogues of 1-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo-[5,6]-cyclohepta[1,2-b]pyridin-11-yl)piperidine as inhibitors of farnesyl protein transferase

被引：8

作者：

Afonso, A ^{[1
]}

Weinstein, J ^{[1
]}

Kelly, J ^{[1
]}

Wolin, R ^{[1
]}

Rosenblum, SB ^{[1
]}

Connolly, M ^{[1
]}

Guzi, T ^{[1
]}

James, L ^{[1
]}

Carr, D ^{[1
]}

Patton, R ^{[1
]}

Bishop, WR ^{[1
]}

Kirshmeier, P ^{[1
]}

Liu, M ^{[1
]}

Heimark, L ^{[1
]}

Chen, KJ ^{[1
]}

Nomeir, AA ^{[1
]}

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1999年 / 7卷 / 09期

关键词：

D O I：

10.1016/S0968-0896(99)00103-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The synthesis of several 4-pyridylacetyl N-oxide derivatives of 4-(3-bromo-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]-pyridin-11-yl)piperazine/piperidine 3 is described. This study was aimed at identifying fomesyl protein transferase (FPT) inhibitors in these two series of tricycles containing different phenyl ring substituents. The in vitro activity profile of the initial group of compounds 7a-7g led to the synthesis of the 8-methyl-10-methoxy and 8-methyl-10-bromo analogues 7i, 13i, and 13j. The 11R(-) enantiomers of these compounds were found to exhibit potent in vitro FPT inhibition activity. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：1845 / 1855

页数：11

共 22 条

[21] DUAL ANTAGONISTS OF PLATELET-ACTIVATING-FACTOR AND HISTAMINE .2. PYRIDINE RING SUBSTITUTION OF N-ACETYL-4-(8-CHLORO-5,6-DIHYDRO-11H-BENZO[5,6]CYCLOHEPTA[1,2-B]PYRIDIN-11-YLIDENE)PIPERIDINES [J].