title: N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors.
abstract: A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin-West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase inhibitor (IC(50)=2.45 μM) as well as the most potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase.
authors.affiliation: Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Chemistry, Indo-Soviet Friendship College of Pharmacy, Moga 142 001, Punjab, India.
authors.forename: Kunal
authors.initials: K
authors.lastname: Nepali
authors.forename: Amit
authors.initials: A
authors.lastname: Agarwal
authors.forename: Sameer
authors.initials: S
authors.lastname: Sapra
authors.forename: Vineet
authors.initials: V
authors.lastname: Mittal
authors.forename: Raj
authors.initials: R
authors.lastname: Kumar
authors.forename: Uttam C
authors.initials: UC
authors.lastname: Banerjee
authors.forename: Manish K
authors.initials: MK
authors.lastname: Gupta
authors.forename: Naresh K
authors.initials: NK
authors.lastname: Satti
authors.forename: Om P
authors.initials: OP
authors.lastname: Suri
authors.forename: Kanaya L
authors.initials: KL
authors.lastname: Dhar
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D014969:Xanthine Oxidase