Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate synthase
Structure-activity relationships of compounds targeting mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate synthase
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DOI：
10.1016/j.bmcl.2008.08.034
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发表时间：
2008-10-01
影响因子：
2.7
通讯作者：
Kozikowski, Alan P.
中科院分区：
文献类型：
--
作者：
Mao, Jialin;Eoh, Hyungjin;Kozikowski, Alan P.
我们报道了一种基于靶点的方法，从已知的转酮醇酶抑制剂的结构中识别可能的结核分枝杆菌DXS抑制剂。为了开始阐明3-(4-氯苯基)-5-苄基4H-吡唑并[1，5-a]嘧啶-7-酮的一些有意义的构效关系，我们建立了一个小的类似物的聚焦文库。最终我们发现2-methyl-3-(4-fluorophenyl)-5-(4-methoxyphenyl)-4H-pyrazolo[1，5-a]pyrimidin-7-one，虽然仍然很弱，但能够抑制结核分枝杆菌DXS，IC_(50)为10.6亩M。(C)2008 Elsevier Ltd.保留所有权利。
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.