5-Heteroatom-substituted pyrazoles as canine COX-2 inhibitors: Part 2. Structure–activity relationship studies of 5-alkylethers and 5-thioethers

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 5; pp. 1202 - 1206
• Main Authors: Sakya, Subas M., Cheng, Hengmiao, Lundy DeMello, Kristin M., Shavnya, Andrei, Minich, Martha L., Rast, Bryson, Dutra, Jason, Li, Chao, Rafka, Robert J., Koss, David A., Li, Jin, Jaynes, Burton H., Ziegler, Carl B., Mann, Donald W., Petras, Carol F., Seibel, Scott B., Silvia, Annette M., George, David M., Hickman, Anne, Haven, Michelle L., Lynch, Michael P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.2006; Elsevier
• Subjects: Aanine; Alkylation; Animals; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; COX-1; COX-2; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacokinetics; Cyclooxygenase 2 Inhibitors - pharmacology; Dogs; Ethers - chemistry; Heteroatom; Inhibitory Concentration 50; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Pyrazoles; Pyrazoles - chemistry; SAR; Structure-Activity Relationship; Sulfhydryl Compounds - chemistry; Heteroatom; COX-2; Pyrazoles; COX-1; SAR; Aanine; Prostaglandin-endoperoxide synthase; Nitrile; Sulfone; Cyclooxygenase 2; Cyclooxygenase 2 inhibitor; Selectivity; Organic sulfide; Pyridine derivatives; Structure activity relation; Pyrazole derivatives; Chemical synthesis; Aanine: SAR; Dog; Fissipedia; Carnivora; Ether; Enzyme; Oral administration; Enzyme inhibitor; In vitro; Non steroidal antiinflammatory agent; In vivo; Vertebrata; Mammalia; Animal; Fluorine Organic compounds; Oxidoreductases; Pharmacokinetics
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.11.110

Structure–activity relationship (SAR) studies of novel 2-[3-trifluoromethyl-5-alkyl(thio)ether pyrazo-1-yl]-5-methanesulfonyl pyridine derivatives for canine COX enzymes are described. The 4-cyano-5-alkyl ethers were found to have excellent potency and selectivity, whereas the 5-thioethers were potent but less selective than the ether analogs in a canine whole blood (CWB) COX-2 assay. Structure–activity relationship (SAR) studies of novel 2-[3-trifluoromethyl-5-alkyl(thio)ether pyrazo-1-yl]-5-methanesulfonyl pyridine derivatives for canine COX enzymes are described. The 4-cyano-5-alkyl ethers were found to have excellent potency and selectivity, whereas the 5-thioethers were potent but less selective than the ether analogs in a canine whole blood (CWB) COX-2 assay.