2. Academic Validation
  3. Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease

Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease

  • Bioorg Med Chem Lett. 2011 Jun 15;21(12):3568-72. doi: 10.1016/j.bmcl.2011.04.125.
Michael O Clarke 1,  Xiaowu Chen,  Aesop Cho,  William E Delaney 4th,  Edward Doerffler,  Maria Fardis,  Mingzhe Ji,  Michael Mertzman,  Rowchanak Pakdaman,  Hyun-Jun Pyun,  Tanisha Rowe,  Cheng Y Yang,  X Christopher Sheng,  Choung U Kim
Affiliations

Affiliation

  • 1 Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA 94404, USA. Michael.Clarke@gilead.com
PMID: 21601450 DOI: 10.1016/j.bmcl.2011.04.125
Abstract

A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationally constraining these compounds through macrocyclization. The syntheses and preliminary biological evaluation of these phosphinic acids is described.

Figures