title: 3-(2-Methoxytetrahydrofuran-2-yl)pyrazoles: a novel class of potent, selective cyclooxygenase-2 (COX-2) inhibitors.
abstract: A series of 3-(2-methoxytetrahydrofuran-2-yl)pyrazoles (4-10) was synthesized. The compounds were evaluated for their ability to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activity in human whole blood (HWB). The compound, 5-(4-methanesulfonylphenyl)-3-(2-methoxytetrahydrofuran-2-yl)-1-p-tolyl-1H-pyrazole 5 showed potent and selective COX-2 inhibition (IC50 for COX-1: >100 microM and COX-2: 1.2 microM).
authors.affiliation: NitroMed Inc., 125 Spring St., Lexington, MA 02421, USA. ramani@nitromed.com
authors.forename: Ramani R
authors.initials: RR
authors.lastname: Ranatunge
authors.forename: Richard A
authors.initials: RA
authors.lastname: Earl
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: David J
authors.initials: DJ
authors.lastname: Schwalb
authors.forename: Delano V
authors.initials: DV
authors.lastname: Young
authors.forename: Irina S
authors.initials: IS
authors.lastname: Zemtseva
mesh_terms: D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood / Q000187:drug effects*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: 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