title: Structure-activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone. The effect of methoxy substitution on aldose reductase inhibitory activity and selectivity.
abstract: Based on our previous work, we studied the effect of methoxy-substitution as well as the regioposition of the benzoyl-moiety of 4a [(1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl)(phenyl)methanone]. On this basis, compounds 4b-c and 5a-c were synthesized and assayed for aldose and aldehyde reductase inhibitory activity. Furthermore, a 4,6-difluoro-5-hydroxyphenyl pattern (9) was studied, in order to verify the optimum position of the phenol-moiety. Compound 5b emerged as the most potent and selective inhibitor. Moreover, further assays proved 5b as a potent antioxidant and an inhibitor of sorbitol accumulation in isolated rat lenses. Combining the above attributes, 5b could serve as a lead compound targeted at long-term diabetes complications.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Chatzopoulou
authors.forename: Eduard
authors.initials: E
authors.lastname: Mamadou
authors.forename: Maria
authors.initials: M
authors.lastname: Juskova
authors.forename: Cathrine
authors.initials: C
authors.lastname: Koukoulitsa
authors.forename: Ioannis
authors.initials: I
authors.lastname: Nicolaou
authors.forename: Milan
authors.initials: M
authors.lastname: Stefek
authors.forename: Vassilis J
authors.initials: VJ
authors.lastname: Demopoulos
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship
chemical_list: C486795:(1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl)phenylmethanone; D004791:Enzyme Inhibitors; D010636:Phenols; D011758:Pyrroles; D000449:Aldehyde Reductase