Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease inhibitors

  • Bioorg Med Chem Lett. 2001 Oct 22;11(20):2683-6. doi: 10.1016/s0960-894x(01)00542-x.
S E Webber  1 ,  J T Marakovits ,  P S Dragovich ,  T J Prins ,  R Zhou ,  S A Fuhrman ,  A K Patick ,  D A Matthews ,  C A Lee ,  B Srinivasan ,  T Moran ,  C E Ford ,  M A Brothers ,  J E Harr ,  J W Meador 3rd ,  R A Ferre ,  S T Worland
Affiliations
  • 1. Pfizer Global Research and Development, La Jolla, 3565 General Atomics Court, San Diego, CA 92121, USA. [email protected]
PMID: 11591501 DOI: 10.1016/s0960-894x(01)00542-x
Abstract

Novel tripeptidyl C-terminal Michael acceptors with an ester replacement of the P(2)-P(3) amide bond were investigated as irreversible inhibitors of the human rhinovirus (HRV) 3C protease (3CP). When screened against HRV serotype-14 the best compound was shown to have very good 3CP inhibition (k(obs)/[I]=270,000M(-1)s(-1)) and potent in vitro Antiviral activity (EC(50)=7.0nM).