Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

Vinay V. Thakur; Joseph T. Kim; Andrew D. Hamilton; Christopher M. Bailey; Robert A. Domaoal; Ligong Wang; Karen S. Anderson; William L. Jorgensen

doi:10.1016/j.bmcl.2006.08.037

Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

Vinay V. Thakur, Joseph T. Kim, Andrew D. Hamilton, Christopher M. Bailey, Robert A. Domaoal, Ligong Wang, Karen S. Anderson, William L. Jorgensen

Chemistry

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

Abstract

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het = 2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties.

Original language	English (US)
Pages (from-to)	5664-5667
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2006.08.037
State	Published - Nov 1 2006

Keywords

2-Pyrimidinylamine
Anti-HIV
Free energy perturbation
NNRTI
Structure-based drug design
Triazinylamine

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2006.08.037

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title = "Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase",

abstract = "Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het = 2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties.",

keywords = "2-Pyrimidinylamine, Anti-HIV, Free energy perturbation, NNRTI, Structure-based drug design, Triazinylamine",

author = "Thakur, {Vinay V.} and Kim, {Joseph T.} and Hamilton, {Andrew D.} and Bailey, {Christopher M.} and Domaoal, {Robert A.} and Ligong Wang and Anderson, {Karen S.} and Jorgensen, {William L.}",

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doi = "10.1016/j.bmcl.2006.08.037",

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AU - Thakur, Vinay V.

AU - Kim, Joseph T.

AU - Hamilton, Andrew D.

AU - Bailey, Christopher M.

AU - Domaoal, Robert A.

AU - Wang, Ligong

AU - Anderson, Karen S.

AU - Jorgensen, William L.

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het = 2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties.

AB - Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het-NH-Ph-U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het = 2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2-20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties.

KW - 2-Pyrimidinylamine

KW - Anti-HIV

KW - Free energy perturbation

KW - NNRTI

KW - Structure-based drug design

KW - Triazinylamine

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Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

Abstract

Keywords

ASJC Scopus subject areas

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