Syntheses and biological activities of sulfoximine-based acyclic triaryl olefins

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 13; pp. 4307 - 4309
• Main Authors: Chen, Xiao Yun, Park, Seong Jun, Buschmann, Helmut, De Rosa, Maria, Bolm, Carsten
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.07.2012; Elsevier
• Subjects: Acyclic triaryl olefin; Alkenes - chemical synthesis; Alkenes - chemistry; Alkenes - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; chemistry; COX-2 selective inhibitor (COXIB); Cyclooxygenase 1 - chemistry; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - chemistry; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - chemical synthesis; Cyclooxygenase Inhibitors - chemistry; Cyclooxygenase Inhibitors - pharmacology; Estrogen receptor; Estrogen Receptor alpha - antagonists & inhibitors; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - antagonists & inhibitors; Estrogen Receptor beta - metabolism; Estrogen receptors; Humans; Imines - chemistry; Medical sciences; olefin; Pharmacology. Drug treatments; Protein Binding - drug effects; Sulfones - chemistry; Sulfoximine; Estrogen receptor; Acyclic triaryl olefin; Sulfoximine; COX-2 selective inhibitor (COXIB); Sulfoximide; Enzyme; Cyclooxygenase 2; Enzyme inhibitor; Cyclooxygenase 2 inhibitor; Selectivity; Biological activity; Non steroidal antiinflammatory agent; Olefin; Oxidoreductases; Chemical synthesis; Ethylenic compound; Hormonal receptor
• ISSN: 0960-894X; 1464-3405; 1464-3405
• DOI: 10.1016/j.bmcl.2012.05.018

Sulfoximine-based acyclic triaryl olefins 8 and 9 have been prepared and initial studies have been performed to determine their biological profiles. In contrast to their sulfonyl-substituted analog 2 sulfoximines 8 and 9 show low COX inhibitory activity. All compounds affect the estrogen receptors. While sulfone 2 interacts exclusively with ER β, sulfoximines 8 and 9 reveal almost equal blocking potencies for both estrogen receptors, ER α and ER β. In the tested series, triaryl olefin 9a shows the highest inhibitory activities with 91% and 80%, respectively (at 10μM).