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

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 containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity.

SUBMITTER: Ghosh AK

PROVIDER: S-EPMC4133278 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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

Ghosh Arun K AK Schiltz Gary E GE Rusere Linah N LN Osswald Heather L HL Walters D Eric DE Amano Masayuki M Mitsuya Hiroaki H

Organic & biomolecular chemistry 20140901 35

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 containing a 16-membered ...[more]

PMID: 25050776

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