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

doi:10.1039/c4ob00738g

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

Chemistry

Research output: Contribution to journal › Article › peer-review

19 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 language	English (US)
Pages (from-to)	6842-6854
Number of pages	13
Journal	Organic and Biomolecular Chemistry
Volume	12
Issue number	35
DOIs	https://doi.org/10.1039/c4ob00738g
State	Published - Sep 21 2014

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ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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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",

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AU - Ghosh, Arun K.

AU - Schiltz, Gary E.

AU - Rusere, Linah N.

AU - Osswald, Heather L.

AU - Walters, D. Eric

AU - Amano, Masayuki

AU - Mitsuya, Hiroaki

PY - 2014/9/21

Y1 - 2014/9/21

N2 - 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

AB - 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

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

Abstract

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UN SDGs

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