Design and synthesis of novel pyrimidone analogues as HIV-1 integrase inhibitors

Shenghui Yu; Tino Wilson Sanchez; Yang Liu; Yanzhen Yin; Nouri Neamati; Guisen Zhao

doi:10.1016/j.bmcl.2013.09.018

Design and synthesis of novel pyrimidone analogues as HIV-1 integrase inhibitors

Shenghui Yu, Tino Wilson Sanchez, Yang Liu, Yanzhen Yin, Nouri Neamati, Guisen Zhao

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

11 Scopus citations

Abstract

A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds could occupy the IN active site and form pi-pi interactions with viral DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3′OH and block intasome activity.

Original language	English (US)
Pages (from-to)	6134-6137
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2013.09.018
State	Published - Nov 15 2013
Externally published	Yes

Keywords

HIV-1
Integrase inhibitors
Pyrimidone analogues

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.2013.09.018

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title = "Design and synthesis of novel pyrimidone analogues as HIV-1 integrase inhibitors",

abstract = "A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds could occupy the IN active site and form pi-pi interactions with viral DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3′OH and block intasome activity.",

keywords = "HIV-1, Integrase inhibitors, Pyrimidone analogues",

author = "Shenghui Yu and Sanchez, {Tino Wilson} and Yang Liu and Yanzhen Yin and Nouri Neamati and Guisen Zhao",

note = "Funding Information: This work was financially supported by the National Natural Science Foundation of China (Nos 20872082 and 21072115 ). The work in the Neamati laboratory was supported by a grant from the Campbell Foundation . ",

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T1 - Design and synthesis of novel pyrimidone analogues as HIV-1 integrase inhibitors

AU - Yu, Shenghui

AU - Sanchez, Tino Wilson

AU - Liu, Yang

AU - Yin, Yanzhen

AU - Neamati, Nouri

AU - Zhao, Guisen

N1 - Funding Information: This work was financially supported by the National Natural Science Foundation of China (Nos 20872082 and 21072115 ). The work in the Neamati laboratory was supported by a grant from the Campbell Foundation .

PY - 2013/11/15

Y1 - 2013/11/15

N2 - A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds could occupy the IN active site and form pi-pi interactions with viral DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3′OH and block intasome activity.

AB - A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds could occupy the IN active site and form pi-pi interactions with viral DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3′OH and block intasome activity.

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KW - Integrase inhibitors

KW - Pyrimidone analogues

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Design and synthesis of novel pyrimidone analogues as HIV-1 integrase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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