Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses

Giang Le; Nick Vandegraaff; David I. Rhodes; Eric D. Jones; Jonathan A V Coates; Long Lu; Xinming Li; Changjiang Yu; Xiao Feng; John J. Deadman

doi:10.1016/j.bmcl.2010.07.041

Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses

Giang Le, Nick Vandegraaff, David I. Rhodes, Eric D. Jones, Jonathan A V Coates, Long Lu, Xinming Li, Changjiang Yu, Xiao Feng, John J. Deadman

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

22 Citations (Scopus)

Abstract

A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.

Original language	English
Pages (from-to)	5013-5018
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2010.07.041
Publication status	Published - 1 Sep 2010
Externally published	Yes

Keywords

HIV
Inhibitor
Integrase
Mutant virus
NHEQ
QHGS
Synthesis

UN SDGs

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

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10.1016/j.bmcl.2010.07.041

Cite this

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title = "Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses",

abstract = "A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.",

keywords = "HIV, Inhibitor, Integrase, Mutant virus, NHEQ, QHGS, Synthesis",

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T1 - Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses

AU - Le, Giang

AU - Vandegraaff, Nick

AU - Rhodes, David I.

AU - Jones, Eric D.

AU - Coates, Jonathan A V

AU - Lu, Long

AU - Li, Xinming

AU - Yu, Changjiang

AU - Feng, Xiao

AU - Deadman, John J.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.

AB - A series of novel HIV integrase inhibitors active against rategravir resistant strains are reported. Initial SAR studies revealed that activities against wild-type virus were successfully maintained at single digit nanomolar level with a wide range of substitutions. However, inclusion of nitrogen-based cyclic substitutions was crucial for achieving potency against mutant viruses. Several compounds with excellent activities against wild-type virus as well as against the viruses with the mutations Q148H/G140S or N155H/E92Q were reported.

KW - HIV

KW - Inhibitor

KW - Integrase

KW - Mutant virus

KW - NHEQ

KW - QHGS

KW - Synthesis

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M3 - Article

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AN - SCOPUS:77955652935

VL - 20

SP - 5013

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 17

ER -

Discovery of potent HIV integrase inhibitors active against raltegravir resistant viruses

Abstract

Keywords

UN SDGs

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