304649-81-8Relevant articles and documents
Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine
Li, Jin,Lundy DeMello, Kristin M.,Cheng, Henry,Sakya, Subas M.,Bronk, Brian S.,Rafka, Robert J.,Jaynes, Burton H.,Ziegler, Carl B.,Kilroy, Carolyn,Mann, Donald W.,Nimz, Eric L.,Lynch, Michael P.,Haven, Michelle L.,Kolosko, Nicole L.,Minich, Martha L.,Li, Chao,Dutra, Jason K.,Rast, Bryson,Crosson, Rhonda M.,Morton, Barry J.,Kirk, Glen W.,Callaghan, Kathleen M.,Koss, David A.,Shavnya, Andrei,Lund, Lisa A.,Seibel, Scott B.,Petras, Carol F.,Silvia, Annette
, p. 95 - 98 (2007/10/03)
Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted.
Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: Identification of 4-[5-(4-methylphenyl)- 3(trifluoromethyl)-1h-pyrazol-1-yl]benzenesulfonamide (sc-58635, celecoxib)
Penning, Thomas D.,Talley, John J.,Bertenshaw, Stephen R.,Carter, Jeffery S.,Collins, Paul W.,Docter, Stephen,Graneto, Matthew J.,Lee, Len F.,Malecha, James W.,Miyashiro, Julie M.,Rogers, Roland S.,Rogier,Yu, Stella S.,Anderson, Gary D.,Burton, Earl G.,Cogburn, J. Nita,Gregory, Susan A.,Koboldt, Carol M.,Perkins, William E.,Seibert, Karen,Veenhuizen, Amy W.,Zhang, Yan Y.,Isakson, Peter C.
, p. 1347 - 1365 (2007/10/03)
A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC- 236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-y1]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.
