Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate synthase

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:18

Article

Mao, Jialin^1,2  Eoh, Hyungjin³  He, Rong¹  Wang, Yuehong²  Wan, Baojie²  Franzblau, Scott G.²  Crick, Dean C.³  Kozikowski, Alan P.¹ 

[1] Univ Illinois, Drug Discovery Program, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA

[2] Univ Illinois, Coll Pharm, Inst TB Res, Chicago, IL 60612 USA

[3] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA

关键词: drug design;    DXS;    enzyme;    SAR;    tuberculosis;   

DOI  :  10.1016/j.bmcl.2008.08.034

来源: Elsevier

【 摘 要 】

We report on a target- based approach to identify possible Mycobacterium tuberculosis DXS inhibitors from the structure of a known transketolase inhibitor. A small focused library of analogs was assembled in order to begin elucidating some meaningful structure - activity relationships of 3-(4-chloro-phenyl)-5-benzyl4H-pyrazolo[ 1,5-a]pyrimidin-7-one. Ultimately we found that 2-methyl-3-(4-fluorophenyl)-5-(4-methoxyphenyl)-4H-pyrazolo[1,5-a]pyrimidin-7-one, although still weak, was able to inhibit M. tuberculosis DXS with an IC50 of 10.6 mu M. (c) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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