title: Synthesis and selective cyclooxygenase-2 (COX-2) inhibitory activity of a series of novel bicyclic pyrazoles.
abstract: Novel series of pyrazolo[5,1-b]1,3-oxazolidines, pyrazolo[5,1-b]1,3-oxazines and imidazolidino[1,2-d]pyrazoles were synthesized. These compounds were evaluated in vitro for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human whole blood (HWB). Several of the compounds were found to be novel and selective COX-2 inhibitors, the most potent and selective being 1-(5-cyclohexyl (2H,3H-pyrazolo[5,1-b]-1,3-oxazolidin-6-yl)-4-(methylsulfonyl)benzene, 7a (IC(5o) for COX-1>100 microM; for COX-2=1.3 microM).
authors.affiliation: NitroMed Inc, 12 Oak Park Drive, Bedford, MA 01730, USA. rbadarage@nitromed.com
authors.forename: Ramani R
authors.initials: RR
authors.lastname: Ranatunge
authors.forename: David S
authors.initials: DS
authors.lastname: Garvey
authors.forename: David R
authors.initials: DR
authors.lastname: Janero
authors.forename: L Gordon
authors.initials: LG
authors.lastname: Letts
authors.forename: Allison M
authors.initials: AM
authors.lastname: Martino
authors.forename: Madhavi G
authors.initials: MG
authors.lastname: Murty
authors.forename: Stewart K
authors.initials: SK
authors.lastname: Richardson
authors.forename: Delano V
authors.initials: DV
authors.lastname: Young
authors.forename: Irina S
authors.initials: IS
authors.lastname: Zemetseva
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases