title: Synthesis and evaluation of 1,5-diaryl-substituted tetrazoles as novel selective cyclooxygenase-2 (COX-2) inhibitors.
abstract: A series of 1,5-diaryl-substituted tetrazole derivatives was synthesized via conversion of readily available diaryl amides into corresponding imidoylchlorides followed by reaction with sodium azide. All compounds were evaluated by cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Tetrazoles 3a-e showed IC(50) values ranging from 0.42 to 8.1 mM for COX-1 and 2.0 to 200 μM for COX-2. Most potent compound 3c (IC(50) (COX-2)=2.0 μM) was further used in molecular modeling docking studies.
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Canada.
authors.forename: Baker Jawabrah
authors.initials: BJ
authors.lastname: Al-Hourani
authors.forename: Sai Kiran
authors.initials: SK
authors.lastname: Sharma
authors.forename: Jonathan Y
authors.initials: JY
authors.lastname: Mane
authors.forename: Jack
authors.initials: J
authors.lastname: Tuszynski
authors.forename: Vickie
authors.initials: V
authors.lastname: Baracos
authors.forename: Torsten
authors.initials: T
authors.lastname: Kniess
authors.forename: Mavanur
authors.initials: M
authors.lastname: Suresh
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
mesh_terms: D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006860:Hydrogen Bonding; D008958:Models, Molecular; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D013777:Tetrazoles