Potent inhibition of Norwalk virus by cyclic sulfamide derivatives

• Published in: Bioorganic & medicinal chemistry Vol. 19; no. 20; pp. 5975 - 5983
• Main Authors: Dou, Dengfeng, Tiew, Kok-Chuan, He, Guijia, Mandadapu, Sivakoteswara Rao, Aravapalli, Sridhar, Alliston, Kevin R., Kim, Yunjeong, Chang, Kyeong-Ok, Groutas, William C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.10.2011; Elsevier
• Subjects: amides; Amides - chemistry; Amides - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; antiviral properties; Biological and medical sciences; Cell Line, Tumor; Humans; Inhibitor; Medical sciences; Molecular Structure; Norwalk virus; Norwalk virus - chemistry; Norwalk virus - drug effects; Pharmacology. Drug treatments; Structure-Activity Relationship; structure-activity relationships; Sulfonic Acids - chemistry; Sulfonic Acids - pharmacology; Inhibitor; Norwalk virus; Virus; Calicivirus; Human calicivirus; Structure activity relation; Sulfonamides; Caliciviridae; Antiviral; Chemical synthesis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2011.08.054

A new class of compounds that exhibit anti-norovirus activity in a cell-based system and embody in their structure a cyclosulfamide scaffold, has been identified. The structure of the initial hit (compound 2a (structure (I) where R = H), ED 50 4 μM, TD 50 50 μM) has been prospected by exploiting multiple points of diversity and generating appropriate structure–activity relationships. A new class of compounds that exhibit anti-norovirus activity in a cell-based system and embody in their structure a cyclosulfamide scaffold has been identified. The structure of the initial hit (compound 2a, ED 50 4 μM, TD 50 50 μM) has been prospected by exploiting multiple points of diversity and generating appropriate structure–activity relationships.