Inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies

…, J Diao, P Chen, V Pujari, Y Yao, G Cheng…

Index: Deng, Lisheng; Diao, Jiasheng; Chen, Pinhong; Pujari, Venugopal; Yao, Yuan; Cheng, Gang; Crick, Dean C.; Prasad, B. V. Venkataram; Song, Yongcheng Journal of Medicinal Chemistry, 2011 , vol. 54, # 13 p. 4721 - 4734

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Citation Number: 45

Abstract

1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (Ec DXR) with a K i of 420 nM. Structure–activity relationships (SAR) are discussed, which ...