Design, synthesis and biological evaluation of cycloalkyl arylpyrimidines (CAPYs) as HIV-1 NNRTIs

Shuang-Xi Gu; Shi-Qiong Yang; Qiu-Qin He; Xiao-Dong Ma; Fen-Er Chen; Hui-Fang Dai; Erik De Clercq; Jan Balzarini; Christophe Pannecouque

doi:10.1016/j.bmc.2011.10.002

Design, synthesis and biological evaluation of cycloalkyl arylpyrimidines (CAPYs) as HIV-1 NNRTIs

Bioorg Med Chem. 2011 Dec 1;19(23):7093-9. doi: 10.1016/j.bmc.2011.10.002. Epub 2011 Oct 7.

Authors

Shuang-Xi Gu¹, Shi-Qiong Yang, Qiu-Qin He, Xiao-Dong Ma, Fen-Er Chen, Hui-Fang Dai, Erik De Clercq, Jan Balzarini, Christophe Pannecouque

Affiliation

¹ Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.

PMID: 22037050
DOI: 10.1016/j.bmc.2011.10.002

Abstract

A series of 18 cycloalkyl arylpyrimidines (CAPYs) were designed from lead compounds diarylpyrimidines (DAPYs), synthesized and evaluated for in vitro anti-HIV activity. Among them, the compound 1p displayed potent anti-HIV-1 activity against WT HIV-1 with an EC(50) value of 0.055 μM and a selectivity index (SI) >7290. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated, which enriched the SAR of diarylpyrimidines (DAPYs).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology
HIV Reverse Transcriptase / antagonists & inhibitors*
HIV Reverse Transcriptase / genetics
HIV Reverse Transcriptase / metabolism
HIV-1 / enzymology*
Humans
Models, Molecular
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology*
Reverse Transcriptase Inhibitors / chemical synthesis
Reverse Transcriptase Inhibitors / chemistry*
Reverse Transcriptase Inhibitors / pharmacology
Structure-Activity Relationship

Substances

Anti-HIV Agents
Pyrimidines
Reverse Transcriptase Inhibitors
reverse transcriptase, Human immunodeficiency virus 1
HIV Reverse Transcriptase