Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors

  • J Med Chem. 2006 Feb 9;49(3):1198-201. doi: 10.1021/jm0507678.
Han-Zhong Zhang  1 ,  Hong Zhang ,  William Kemnitzer ,  Ben Tseng ,  Jindrich Cinatl Jr ,  Martin Michaelis ,  Hans Wilhelm Doerr ,  Sui Xiong Cai
Affiliations
  • 1. Maxim Pharmaceuticals, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.
PMID: 16451084 DOI: 10.1021/jm0507678
Abstract

This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.