Antiinflammatory 2-benzyl-4-sulfonyl-4H-isoquinoline-1,3-diones: Novel inhibitors of COX-2

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 10; pp. 1181 - 1186
• Main Authors: LAZER, E. S, SORCEK, R, CYWIN, C. L, THOME, D, POSSANZA, G. J, GRAHAM, A. G, CHURCHILL, L
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 19-05-1998
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Carrageenan; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - chemical synthesis; Cyclooxygenase Inhibitors - chemistry; Cyclooxygenase Inhibitors - pharmacology; Edema - chemically induced; Edema - drug therapy; Isoenzymes - metabolism; Isoquinolines - chemical synthesis; Isoquinolines - chemistry; Isoquinolines - pharmacology; Kinetics; Medical sciences; Membrane Proteins; Microsomes - enzymology; Molecular Structure; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Structure-Activity Relationship; Prostaglandin-endoperoxide synthase; Rat; Sulfone; Enzyme; Nitrogen heterocycle; Isozyme; Rodentia; Antiinflammatory agent; Oral administration; Enzyme inhibitor; Quinoline derivatives; In vitro; Imide; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Structure activity relation; Animal; Chlorine Organic compounds; Oxidoreductases; Fluorine Organic compounds; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00184-X

A series of 2-benzyl-4-sulfonyl-4H-isoquinoline-1,3-diones was prepared. Members of this series are potent and selective inhibitors of cyclooxygenase-2 (COX-2) in both microsomal and cellular assays. Two representatives demonstrated activity in the carrageenan-induced paw edema model in rats upon oral administration.