Combinatorial modification of natural products:: Synthesis and in vitro analysis of derivatives of thiazole peptide antibiotic GE2270 A:: A-ring modifications

被引：51

作者：

Clough, J

Chen, SQ

Gordon, EM

Hackbarth, C

Lam, S

Trias, J

White, RJ

Candiani, G

Donadio, S

Romanò, G

Ciabatti, R

Jacobs, JW

机构：

[1] Vicuron Inc, Fremont, CA 94555 USA

[2] Vicuron Inc, I-21040 Gerenzano, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(03)00811-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Thiazole peptide GE2270 A (1) possesses potent antimicrobial activity against many gram-positive pathogens, including methicillin resistant Staphylococcus aureus (S. aureus, MRSA; MIC90=0.06 mug/mL) and vancomycin resistant Enterococcus spp. (VRE; MIC90=0.03 mug/mL); however its poor aqueous solubility has prohibited its development for the clinical treatment of infections. An integrated combinatorial and medicinal chemistry program was employed to identify derivatives of 1 that retain activity but possess greatly enhanced aqueous solubility. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：3409 / 3414

页数：6

共 18 条

[1] NEW ANTIBIOTIC THAT ACTS SPECIFICALLY ON THE GTP-BOUND FORM OF ELONGATION FACTOR-TU [J].