New C25 carbamate rifamycin derivatives are resistant to inactivation by ADP-ribosyl transferases

被引：32

作者：

Combrink, Keith D.

Denton, Daniel A.

Harran, Susan

Ma, Zhenkun

Chapo, Katrina

Yan, Dalai

Bonventre, Eric

Roche, Eric D.

Doyle, Timothy B.

Robertson, Gregory T.

Lynch, Anthony S.

机构：

[1] Cumbre Pharmaceut Inc, Dept Chem, Dallas, TX 75235 USA

[2] Cumbre Pharmaceut Inc, Dept Microbiol, Dallas, TX 75235 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 02期

关键词：

rifamycin; ADP-ribosyl transferase; Mycobacterium smegmatis; inactivation;

D O I：

10.1016/j.bmcl.2006.10.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 3-morpholino rifamycins in which the C25 acetate group was replaced by a carbamate group were prepared and found to exhibit-significantly improved antimicrobial activity than rifampin against Mycobacterium smegmatis. Further characterization of such compounds suggests that relatively large groups attached to the rifamycin core via a C25 carbarnate linkage prevent inactivation via ribosylation of the C23 alcohol as catalyzed by the endogenous rifampin ADP-ribosyl transferase of M. smegmatis. SAR studies of the C25 carbarnate rifamycin series against M. smegmatis and other bacteria are reported. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：522 / 526

页数：5

共 20 条

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