title: Design and synthesis of N-alkyldeoxynojirimycin derivatives with improved metabolic stability as inhibitors of BVDV and Tacaribe virus.
abstract: 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.
authors.affiliation: Institute for Hepatitis and Virus Research, 3805 Old Easton Road, Doylestown, PA 18902, USA. yanming.du@ihvr.org
authors.forename: Yanming
authors.initials: Y
authors.lastname: Du
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Tina
authors.initials: T
authors.lastname: Gill
authors.forename: Noshena
authors.initials: N
authors.lastname: Khan
authors.forename: Andrea
authors.initials: A
authors.lastname: Cuconati
authors.forename: Ju-Tao
authors.initials: JT
authors.lastname: Guo
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Block
authors.forename: Jinhong
authors.initials: J
authors.lastname: Chang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xu
mesh_terms: D017485:1-Deoxynojirimycin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006477:Arenaviruses, New World / Q000502:physiology*; D001908:Diarrhea Viruses, Bovine Viral / Q000502:physiology*; D015195:Drug Design; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D023303:Oxazolidinones / Q000737:chemistry; D051381:Rats; D013449:Sulfonamides / Q000737:chemistry; D014508:Urea / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D023303:Oxazolidinones; D013449:Sulfonamides; C501633:deoxynojirimycine; D017485:1-Deoxynojirimycin; D014508:Urea; D005944:Glucosamine