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Design and synthesis of N-alkyldeoxynojirimycin derivatives with improved metabolic stability as inhibitors of BVDV and Tacaribe virus
Journal article   Peer reviewed

Design and synthesis of N-alkyldeoxynojirimycin derivatives with improved metabolic stability as inhibitors of BVDV and Tacaribe virus

Yanming Du, Hong Ye, Fang Guo, Lijuan Wang, Tina Gill, Noshena Khan, Andrea Cuconati, Ju-Tao Guo, Timothy M Block, Jinhong Chang, …
Bioorganic & medicinal chemistry letters, v 23(14), pp 4258-4262
15 Jul 2013
PMID: 23747225

Abstract

1-Deoxynojirimycin - chemistry 1-Deoxynojirimycin - metabolism 1-Deoxynojirimycin - pharmacology Animals Antiviral Agents - chemical synthesis Antiviral Agents - metabolism Antiviral Agents - pharmacology Arenaviruses, New World - physiology Diarrhea Viruses, Bovine Viral - physiology Drug Design Glucosamine - analogs & derivatives Glucosamine - chemistry Glucosamine - metabolism Glucosamine - pharmacology Humans Mice Microsomes, Liver - metabolism Oxazolidinones - chemistry Rats Sulfonamides - chemistry Urea - chemistry Virus Replication - drug effects
Novel N-alkyldeoxynojirimycins (NADNJs) based on our previous lead 3 were designed, synthesized and tested in metabolic assays and in virus cultures. NADNJs containing terminal tertiary benzamide, sulfonamide, urea, and oxazolidinone moieties were discovered to have improved metabolic stability compared to 3, while maintaining submicromolar EC50 against BVDV and Tacaribe virus; and low cytotoxicity.

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Web of Science research areas
Chemistry, Medicinal
Chemistry, Organic
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