Design and synthesis of potent macrocyclic HIV-1 protease inhibitors involving P1-P2 ligands

Arun K. Ghosh*, Gary E. Schiltz, Linah N. Rusere, Heather L. Osswald, D. Eric Walters, Masayuki Amano, Hiroaki Mitsuya

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

A series of potent macrocyclic HIV-1 protease inhibitors have been designed and synthesized. The compounds incorporated 16- to 19-membered macrocyclic rings between a nelfinavir-like P2 ligand and a tyrosine side chain containing a hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent than their corresponding acyclic counterparts. Saturated derivatives showed slight reduction of potency compared to the respective unsaturated derivatives. Compound 8a containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity. This journal is

Original languageEnglish (US)
Pages (from-to)6842-6854
Number of pages13
JournalOrganic and Biomolecular Chemistry
Volume12
Issue number35
DOIs
StatePublished - Sep 21 2014

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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