β-lactam derivatives as inhibitors of human cytomegalovirus protease

被引：80

作者：

Yoakim, C ^{[1
]}

Ogilvie, WW ^{[1
]}

Cameron, DR ^{[1
]}

Chabot, C ^{[1
]}

Guse, I ^{[1
]}

Haché, B ^{[1
]}

Naud, J ^{[1
]}

O'Meara, JA ^{[1
]}

Plante, R ^{[1
]}

Déziel, R ^{[1
]}

机构：

[1] Boehringer Ingelheim Canada Ltd, Biomega Res Div, Laval, PQ H7S 2G5, Canada

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 15期

关键词：

D O I：

10.1021/jm980131z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The development of novel monobactam inhibitors of HCMV protease incorporating a carbon side chain at C-4 and a urea function at N-1 is described. Substitution with small groups at the C-3 position of the beta-lactam ring gave an increase in enzymatic activity and in stability; however, a lack of selectivity against other serine proteases was noted. The use of both tri- and tetrasubstituted urea functionalities gave effective inhibitors of HCMV protease. Benzyl substitution of the urea moiety was beneficial, especially when strong electron-withdrawing groups where attached at the para position. Modest antiviral activity was found in a plaque reduction assay.

引用

页码：2882 / 2891

页数：10

共 33 条

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