Oseltamivir hydroxamate and acyl sulfonamide derivatives as influenza neuraminidase inhibitors

  • Bioorg Med Chem. 2014 Dec 1;22(23):6647-6654. doi: 10.1016/j.bmc.2014.10.005.
Bei-Tao Hong  1 ,  Chun-Lin Chen  1 ,  Jim-Min Fang  2 ,  Keng-Chang Tsai  3 ,  Shi-Yun Wang  4 ,  Wen-I Huang  4 ,  Yih-Shyun E Cheng  4 ,  Chi-Huey Wong  4
Affiliations
  • 1. Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.
  • 2. Department of Chemistry, National Taiwan University, Taipei 106, Taiwan; The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan. Electronic address: [email protected].
  • 3. National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, Taiwan.
  • 4. The Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
PMID: 25456388 DOI: 10.1016/j.bmc.2014.10.005
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).