Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P′2-ligands

Arun K. Ghosh; Gary Schiltz; Ramu Sridhar Perali; Sofiya Leshchenko; Stephanie Kay; D. Eric Walters; Yasuhiro Koh; Kenji Maeda; Hiroaki Mitsuya

doi:10.1016/j.bmcl.2006.01.011

Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P′₂-ligands

Arun K. Ghosh^*, Gary Schiltz, Ramu Sridhar Perali, Sofiya Leshchenko, Stephanie Kay, D. Eric Walters, Yasuhiro Koh, Kenji Maeda, Hiroaki Mitsuya

^*Corresponding author for this work

Chemistry

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

105 Scopus citations

Abstract

A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.

Original language	English (US)
Pages (from-to)	1869-1873
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2006.01.011
State	Published - Apr 1 2006

Keywords

Design
HIV proptease
Inhibitors
Oxyindole
Synthesis
TMC-114

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmaceutical Science
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmcl.2006.01.011

Cite this

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title = "Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P′2-ligands",

abstract = "A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.",

keywords = "Design, HIV proptease, Inhibitors, Oxyindole, Synthesis, TMC-114",

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note = "Funding Information: Financial support by the National Institutes of Health (GM 53386) is gratefully acknowledged. ",

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T1 - Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P′2-ligands

AU - Ghosh, Arun K.

AU - Schiltz, Gary

AU - Perali, Ramu Sridhar

AU - Leshchenko, Sofiya

AU - Kay, Stephanie

AU - Walters, D. Eric

AU - Koh, Yasuhiro

AU - Maeda, Kenji

AU - Mitsuya, Hiroaki

N1 - Funding Information: Financial support by the National Institutes of Health (GM 53386) is gratefully acknowledged.

PY - 2006/4/1

Y1 - 2006/4/1

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AB - A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.

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KW - HIV proptease

KW - Inhibitors

KW - Oxyindole

KW - Synthesis

KW - TMC-114

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