6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase

Jing Tang; Kasthuraiah Maddali; Christine D. Dreis; Yuk Y. Sham; Robert Vince; Yves Pommier; Zhengqiang Wang

doi:10.1016/j.bmcl.2011.02.069

6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase

Jing Tang
, Kasthuraiah Maddali
, Christine D. Dreis
, Yuk Y. Sham
, Robert Vince
, Yves Pommier
, Zhengqiang Wang

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

46 Scopus citations

Abstract

N-3-Hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development.

Original language	English (US)
Pages (from-to)	2400-2402
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2011.02.069
State	Published - Apr 15 2011

Bibliographical note

Funding Information:
This research was supported by the Center for Drug Design at the University of Minnesota, by the Center for Cancer Research, National Cancer Institute, NIH, and by an NIH-IATAP grant to Y.P. and K.M. We thank Roger Ptak at Southern Research Institute for antiviral assays and the Minnesota Supercomputing Institute for modeling resources.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

6-Benzoyl-3-hydroxypyrimidine-2,4-diones
Dual inhibitors
HIV
Integrase
Reverse transcriptase

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10.1016/j.bmcl.2011.02.069

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title = "6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase",

abstract = "N-3-Hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development.",

keywords = "6-Benzoyl-3-hydroxypyrimidine-2,4-diones, Dual inhibitors, HIV, Integrase, Reverse transcriptase",

author = "Jing Tang and Kasthuraiah Maddali and Dreis, \{Christine D.\} and Sham, \{Yuk Y.\} and Robert Vince and Yves Pommier and Zhengqiang Wang",

note = "Funding Information: This research was supported by the Center for Drug Design at the University of Minnesota, by the Center for Cancer Research, National Cancer Institute, NIH, and by an NIH-IATAP grant to Y.P. and K.M. We thank Roger Ptak at Southern Research Institute for antiviral assays and the Minnesota Supercomputing Institute for modeling resources. ",

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doi = "10.1016/j.bmcl.2011.02.069",

language = "English (US)",

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AU - Tang, Jing

AU - Maddali, Kasthuraiah

AU - Dreis, Christine D.

AU - Sham, Yuk Y.

AU - Vince, Robert

AU - Pommier, Yves

AU - Wang, Zhengqiang

N1 - Funding Information: This research was supported by the Center for Drug Design at the University of Minnesota, by the Center for Cancer Research, National Cancer Institute, NIH, and by an NIH-IATAP grant to Y.P. and K.M. We thank Roger Ptak at Southern Research Institute for antiviral assays and the Minnesota Supercomputing Institute for modeling resources.

PY - 2011/4/15

Y1 - 2011/4/15

N2 - N-3-Hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development.

AB - N-3-Hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development.

KW - 6-Benzoyl-3-hydroxypyrimidine-2,4-diones

KW - Dual inhibitors

KW - HIV

KW - Integrase

KW - Reverse transcriptase

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ER -

6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase

Abstract

Bibliographical note

UN SDGs

Keywords

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