title: Design and synthesis of a new series of cyclopropylamino-linking diarylpyrimidines as HIV non-nucleoside reverse transcriptase inhibitors.
abstract: A new series of 29 diarylpyrimidine analogues featuring a cyclopropylamino group between the pyrimidine scaffold and the aryl wing have been synthesized. All of the new compounds have been characterized by spectra analysis. The target molecules were evaluated for their in vitro anti-HIV activity with FDA-approved drugs as references. Some of the compounds exhibited moderate to potent activities against wild-type HIV-1. The compound 4-((4-((cyclopropylamino)(2,5-difluorophenyl)methyl)pyrimidin-2-yl)amino)benzonitrile (1e) displayed potent anti-HIV-1 activity against WT HIV-1 with an IC50 of 0.099 μM and a selectivity index of 2302. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated.
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors: Yang
authors: Y
authors: Liu
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: mengge@mail.xjtu.edu.cn.
authors: Ge
authors: G
authors: Meng
authors: School of Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China.
authors: Aqun
authors: A
authors: Zheng
authors: Department of Chemistry, Fudan University Research, Shanghai 200433, PR China.
authors: Fener
authors: F
authors: Chen
authors: Department of Chemistry, Fudan University Research, Shanghai 200433, PR China.
authors: Wenxue
authors: W
authors: Chen
authors: Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
authors: Erik
authors: E
authors: De Clercq
authors: Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
authors: Christophe
authors: C
authors: Pannecouque
authors: Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
authors: Jan
authors: J
authors: Balzarini
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors
keywords: Anti-HIV activity; Cyclopropylamine; Cyclopropylamine (PubChem CID: 24847670); Diarylpyrimidine; Non-nucleoside RT inhibitors; SAR