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)

Citations Over TimeTop 1% of 1997 papers

Abstract

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)- H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

Related Papers

• → Preparation and Evaluation of Amino Acid Conjugates of Celecoxib as Prodrugs to Improve the Pharmacokinetic and Therapeutic Properties of Celecoxib(2020)53 cited
• → Do proton‐pump inhibitors confer additional gastrointestinal protection in patients given celecoxib?(2007)46 cited
• → Celecoxib and Heterotopic Bone Formation After Total Hip Arthroplasty(2013)45 cited
• → N-Succinylaspart-1-yl Celecoxib is a Potential Colon-Specific Prodrug of Celecoxib with Improved Therapeutic Properties(2012)15 cited
• Celecoxib vs ibuprofen in treating osteoarthritis(2002)