Anthranilate 4H-oxazol-5-ones:: novel small molecule antibacterial acyl carrier protein synthase (AcpS) inhibitors

被引：23

作者：

Gilbert, AM

Kirisits, M

Toy, P

Nunn, DS

Failli, A

Dushin, EG

Novikova, E

Petersen, PJ

Joseph-McCarthy, D

McFadyen, L

Fritze, CC

机构：

[1] Wyeth Res, Dept Chem & Screening Sci, Pearl River, NY 10945 USA

[2] Wyeth Ayerst Res, Dept Chem & Screening Sci, Princeton, NJ 08852 USA

[3] Wyeth Res, Dept Infect Dis Res, Pearl River, NY 10945 USA

[4] Wyeth Res, Dept Chem & Screening Sci, Cambridge, MA 02140 USA

[5] Millennium Pharmaceut Inc, Cambridge, MA 02140 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 01期

关键词：

D O I：

10.1016/j.bmcl.2003.10.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

D-optimal design and Projection to Latent Structures (PLS) analysis were used to optimize screening hit 5 (B. subtilis AcpS IC50: 15 muM, B. subtilis MIC: >200 muM) into a series of 4H-oxazol-5-one, small molecule, antibacterial, AcpS inhibitors. Specifically, 15, 16 and 18 show muM or sub-muM AcpS inhibition (IC(50)s: 15: 1.1 muM, 16: 1.5 muM, 18: 0.27 muM) and moderate antibacterial activity (MICs: 12.5-50 muM) against B. subtilis, E. faecalis ATCC, E. faecalis VRE and S. pneumo(+). (C) 2003 Elsevier Ltd. All rights reserved.

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页码：37 / 41

页数：5

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