title: 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone as a potent and orally active cyclooxygenase-2 selective inhibitor: synthesis and biological evaluation.
abstract: Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase-2 (COX-2) selective inhibitor core structure, 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone (20), with COX-2 IC50 = 0.25 microM and COX-1 IC50 = 14 microM (human whole blood assay). Compound 20 was orally active in the rat air pouch model of inflammation, inhibiting white blood cell infiltration and COX-2-derived PG production. Our data support the identification of a novel COX-2 selective inhibitor core structure exemplified by 20.
authors.affiliation: NitroMed, Inc., 125 Spring Street, Lexington, Massachusetts 02421, USA. skhanapure@nitromed.com
authors.forename: Subhash P
authors.initials: SP
authors.lastname: Khanapure
authors.forename: Michael E
authors.initials: ME
authors.lastname: Augustyniak
authors.forename: Richard A
authors.initials: RA
authors.lastname: Earl
authors.forename: David S
authors.initials: DS
authors.lastname: Garvey
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: David J
authors.initials: DJ
authors.lastname: Schwalb
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Shumway
authors.forename: Andrzej M
authors.initials: AM
authors.lastname: Trocha
authors.forename: Delano V
authors.initials: DV
authors.lastname: Young
authors.forename: Irina S
authors.initials: IS
authors.lastname: Zemtseva
authors.forename: David R
authors.initials: DR
authors.lastname: Janero
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002351:Carrageenan; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C501706:3-(4-(methylsulfonyl)phenyl)-5-(trifluoromethyl)(2-pyridyl) phenyl ketone; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011725:Pyridines; D013450:Sulfones; D002351:Carrageenan; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone