Chiral resolution, determination of absolute configuration, and biological evaluation of (1, 2-benzothiazin-4-yl)acetic acid enantiomers as aldose reductase inhibitors. (October 2015)

• Record Type: Journal Article
• Authors: Hao, Xin; Qin, Xiangyu; Hussain, Saghir; Parveen, Shagufta; Zhang, Wei; Fu, Fengyan; Ma, Bing; Zhu, Changjin
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 30:Number 5(2015:Oct.)
• Page Start: 846
• Page End: 851
• Publication Date: 2015-10
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title>Abstract</title> <p>A novel series of (1, 2-benzothiazin-4-yl)acetic acid enantiomers was prepared by chiral resolution, and their absolute configurations were determined using the PGME method. The biological evaluation of the racemate and single enantiomers has shown a remarkable difference for the aldose reductase inhibitory activity and selectivity. The (R)-(−)-enantiomer exhibited the strongest aldose reductase activity with an IC₅₀ value of 0.120 μM, which was 35 times more active than the S-(+)-enantiomer. Thus, the stereocenter at the C4 position of this scaffold was shown to have a major impact on the activity and selectivity.</p> </abstract>