title: Chiral resolution, determination of absolute configuration, and biological evaluation of (1,2-benzothiazin-4-yl)acetic acid enantiomers as aldose reductase inhibitors.
abstract: 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 IC(50) 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.
authors.affiliation: a Department of Applied Chemistry , Beijing Institute of Technology , Beijing , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hao
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Qin
authors.forename: Saghir
authors.initials: S
authors.lastname: Hussain
authors.forename: Shagufta
authors.initials: S
authors.lastname: Parveen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Fengyan
authors.initials: F
authors.lastname: Fu
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
authors.forename: Changjin
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000085:Acetates; D004791:Enzyme Inhibitors; D013843:Thiazines; D000449:Aldehyde Reductase
keywords: 1,2-benzothiazine 1,1-dioxide; Absolute configuration determination; aldose reductase inhibitors; chiral resolution