title: A rational approach for the design and synthesis of 1-acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles as a new class of potential non-purine xanthine oxidase inhibitors.
abstract: Xanthine oxidase is a complex molybdoflavoprotein that catalyses the hydroxylation of xanthine to uric acid. Fifty three analogues of 1-acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles were rationally designed and synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. Six compounds 41, 42, 44, 46, 55 and 59 were found to be most active against XO with IC(50) ranging from 5.3 μM to 15.2 μM. The compound 59 emerged as the most potent XO inhibitor (IC(50)=5.3 μM). Some of the important interactions of 59 with the amino acid residues of active site of XO have been figured out by molecular modeling.
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: Gurinderdeep
authors.initials: G
authors.lastname: Singh
authors.forename: Anil
authors.initials: A
authors.lastname: Turan
authors.forename: Amit
authors.initials: A
authors.lastname: Agarwal
authors.forename: Sameer
authors.initials: S
authors.lastname: Sapra
authors.forename: Raj
authors.initials: R
authors.lastname: Kumar
authors.forename: Uttam C
authors.initials: UC
authors.lastname: Banerjee
authors.forename: Prabhakar K
authors.initials: PK
authors.lastname: Verma
authors.forename: Naresh K
authors.initials: NK
authors.lastname: Satti
authors.forename: Manish K
authors.initials: MK
authors.lastname: Gupta
authors.forename: Om P
authors.initials: OP
authors.lastname: Suri
authors.forename: K L
authors.initials: KL
authors.lastname: Dhar
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007536:Isomerism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D014969:Xanthine Oxidase