title: Oseltamivir hydroxamate and acyl sulfonamide derivatives  as influenza neuraminidase inhibitors.
abstract: Tamiflu, the ethyl ester form of oseltamivir carboxylic acid (OC), is the first orally available anti-influenza drug for the front-line therapeutic option. In this study, the OC-hydroxamates, OC-sulfonamides and their guanidino congeners (GOC) were synthesized. Among them, an OC-hydroxamate 7d bearing an O-(2-indolyl)propyl substituent showed potent NA inhibition (IC50 = 6.4 nM) and good anti-influenza activity (EC50 = 60.1 nM) against the wild-type H1N1 virus. Two GOC-hydroxamates (9b and 9d) and one GOC-sulfonamide (12a) were active to the tamiflu-resistant H275Y virus (EC50 = 2.3-6.9 μM).
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Bei-Tao
authors.initials: BT
authors.lastname: Hong
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei 106, Taiwan; The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan. Electronic address: jmfang@ntu.edu.tw.
authors.forename: Jim-Min
authors.initials: JM
authors.lastname: Fang
authors.affiliation: National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, Taiwan.
authors.forename: Keng-Chang
authors.initials: KC
authors.lastname: Tsai
authors.affiliation: The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Shi-Yun
authors.initials: SY
authors.lastname: Wang
authors.affiliation: The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Huang
authors.affiliation: The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yih-Shyun E
authors.initials: YE
authors.lastname: Cheng
authors.affiliation: The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C000601696:N-(3-(1H-Indol-2-yl)propoxy) 4-acetamido-5-guanidino-3-(1-ethylpropoxy)-1-cyclohexenecarboxamide; C000601695:N-methoxy 4-acetamido-5-guanidino-3-(1-ethylpropoxy)-1-cyclohexenecarboxamide; C000601697:N-methylsulfonyl 4-acetamido-5-guanidino-3-(1-ethylpropoxy)-1-cyclohexenecarboxamide; D013449:Sulfonamides; D053139:Oseltamivir; D009439:Neuraminidase