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

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)5664-5667
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number21
DOIs
StatePublished - Nov 1 2006

Fingerprint

Cytotoxicity
Amines
Pharmacology
Derivatives
Human immunodeficiency virus 1 reverse transcriptase

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase. / Thakur, Vinay V.; Kim, Joseph T.; Hamilton, Andrew; Bailey, Christopher M.; Domaoal, Robert A.; Wang, Ligong; Anderson, Karen S.; Jorgensen, William L.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 21, 01.11.2006, p. 5664-5667.

Research output: Contribution to journalArticle

Thakur, Vinay V. ; Kim, Joseph T. ; Hamilton, Andrew ; Bailey, Christopher M. ; Domaoal, Robert A. ; Wang, Ligong ; Anderson, Karen S. ; Jorgensen, William L. / Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase. In: Bioorganic and Medicinal Chemistry Letters. 2006 ; Vol. 16, No. 21. pp. 5664-5667.
@article{acd0caf6912f4cb8a35e9b9607aa668a,
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 Andrew Hamilton and Bailey, {Christopher M.} and Domaoal, {Robert A.} and Ligong Wang and Anderson, {Karen S.} and Jorgensen, {William L.}",
year = "2006",
month = "11",
day = "1",
doi = "10.1016/j.bmcl.2006.08.037",
language = "English (US)",
volume = "16",
pages = "5664--5667",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "21",

}

TY - JOUR

T1 - Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

AU - Thakur, Vinay V.

AU - Kim, Joseph T.

AU - Hamilton, Andrew

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

UR - http://www.scopus.com/inward/record.url?scp=33748788858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748788858&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2006.08.037

DO - 10.1016/j.bmcl.2006.08.037

M3 - Article

VL - 16

SP - 5664

EP - 5667

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 21

ER -