synthesis and activity of a new series of(z)-3-phenyl-2-benzoylpropenoic acid derivatives as aldose reductase inhibitors合成和新系列的活动(z)3-phenyl-2-benzoylpropenoic酸衍生物的醛糖还原酶抑制剂.pdf

Molecules 2007, 12, 885-895 molecules ISSN 1420-3049 © 2007 by MDPI /molecules Full Paper Synthesis and Activity of a New Series of (Z)-3-Phenyl-2-benzoylpropenoic Acid Derivatives as Aldose Reductase Inhibitors Shao-Jie Wang 1,*, Ju-Fang Yan 2, Dong Hao 1, Xin-Wen Niu 1 and Mao-Sheng Cheng 1 1 Key Laboratory of New Drugs Design and Discovery of Liaoning Province, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China 2 Drug Screening Center, Di Ao Pharmaceutical Group, Chengdu 123388, P.R. China * Author to whom correspondence should be addressed; E-mail: sjwang_99@; Tel: (+86)24 Fax: (+86)24 Received: 21 March 2007; in revised form: 23 April 2007 / Accepted: 23 April 2007 / Published: 30 April 2007 Abstract: During the course of studies directed towards the discovery of novel aldose reductase inhibitors for the treatment of diabetic complications, we synthesized a series of new (Z)-3-phenyl-2-benzoylpropenoic acid derivatives and tested their in vitro inhibitory activities on rat lens aldose reductase. Of these compounds, (Z)-3-(3,4-dihydroxyphenyl)- 2-(4-methylbenzoyl)propenoic acid (3k) was identified as the most potent inhibitor, with an IC50 of 0.49µM. The theoretical binding mode of 3k was obtained by simulation of its docking into the active site of the human aldose reductase crystal structure. Keywords: (Z)-3-Phenyl-2-benzoylpropenoic acid, aldose reductase inhibitor, structure- activity relationships Introduction Aldose reductase (ALR2