Bioactive sulfoximines: Syntheses and properties of Vioxx® analogs

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 16; pp. 4888 - 4890
• Main Authors: Park, Seong Jun, Buschmann, Helmut, Bolm, Carsten
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.08.2011; Elsevier
• Subjects: bioactive properties; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; chemical derivatives; COX-2-selective inhibitor (COXIB); Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacology; Dose-Response Relationship, Drug; enzyme inhibition; enzyme inhibitors; Ether-A-Go-Go Potassium Channels - antagonists & inhibitors; HEK293 Cells; hERG activity; Humans; Lactones - chemical synthesis; Lactones - chemistry; Lactones - pharmacology; Medical sciences; Methionine Sulfoximine - analogs & derivatives; Methionine Sulfoximine - chemistry; Methionine Sulfoximine - pharmacology; Molecular Structure; Pharmacology. Drug treatments; prostaglandin synthase; Stereoisomerism; Structure-Activity Relationship; structure-activity relationships; Sulfones - chemical synthesis; Sulfones - chemistry; Sulfones - pharmacology; Sulfoximine; synthesis; Vioxx® (Rofecoxib); hERG activity; Vioxx® (Rofecoxib); COX-2-selective inhibitor (COXIB); Sulfoximine; Sulfoximide; Prostaglandin-endoperoxide synthase; Rofecoxib; Enzyme; Toxicity; Cyclooxygenase 2; Benzene derivatives; Enzyme inhibitor; Lactone; Ionic channel; Cyclooxygenase 2 inhibitor; Selectivity; Oxygen heterocycle; In vitro; Non steroidal antiinflammatory agent; Structure activity relation; Oxidoreductases; Circulatory system; Chemical synthesis
• ISSN: 0960-894X; 1464-3405; 1464-3405
• DOI: 10.1016/j.bmcl.2011.06.029

The syntheses and biological profiles of sulfoximine-based Vioxx® analogs 2 are described. Interesting data have been obtained for 2a, which shows a selective COX-2 inhibition (albeit not as strong as Vioxx® itself) exhibiting reduced hERG activity compare to the parent sulfone Vioxx® (1).