title: Synthesis and biological evaluation of novel pyrazole compounds.
abstract: A novel dipyrazole ethandiamide compound and acid chloride of pyrazolo[3,4-d]pyrimidine 4(5H)-one were prepared and reacted with a number of nucleophiles. The resultant novel compounds were tested in several in vitro and in vivo assays. Three compounds inhibited the secretion of neurotoxins by human THP-1 monocytic cells at concentrations that were not toxic to these cells. They also partially inhibited both cyclooxygenase-1 and -2 isoforms. In animal studies, two compounds were notable for their anti-inflammatory activity that was comparable to that of the clinically available cyclooxygenase-2 inhibitor celecoxib. Modeling studies by using the molecular operating environment module showed comparable docking scores for the two enantiomers docked in the active site of cyclooxygenase-2.
authors.affiliation: Department of Chemistry, University of British Columbia Okanagan, Kelowna, BC, Canada.
authors.forename: Amal M
authors.initials: AM
authors.lastname: Youssef
authors.forename: Edward G
authors.initials: EG
authors.lastname: Neeland
authors.forename: Erika B
authors.initials: EB
authors.lastname: Villanueva
authors.forename: M Sydney
authors.initials: MS
authors.lastname: White
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: El-Ashmawy
authors.forename: Brian
authors.initials: B
authors.lastname: Patrick
authors.forename: Andis
authors.initials: A
authors.lastname: Klegeris
authors.forename: Alaa S
authors.initials: AS
authors.lastname: Abd-El-Aziz
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D020134:Catalytic Domain; D000068579:Celecoxib; D002460:Cell Line; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013449:Sulfonamides / Q000737:chemistry / Q000633:toxicity
chemical_list: C553153:2-methylbenzylamino 2-oxo-N-(4-cyano-1-phenyl-1H-pyrazol-5-yl)acetamide; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; C553154:N1,N2-bis(4-cyano-1-phenyl-1H-pyrazol-5-yl)oxalamide; D011720:Pyrazoles; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib