Structural modifications of diarylpyrimidines (DAPYs) as HIV-1 NNRTIs: Synthesis, anti-HIV activities and SAR.
30 new analogues of diarylpyrimidines were synthesized for further structural modifications, involving not only the linker but also the wing α of DAPYs. The anti-HIV-1 activities of all target molecules were evaluated, and most of them exhibited potent anti-HIV-1 (WT) activities and low cytotoxicities. Among which, compound 4g showed excellent activities against WT HIV-1 with an EC50value of 5.8nM and SI of up to 26,034. Another compound 4ab bearing a novel pyridinyl Wing α also displayed attractive activities. The structure-activity relationship (SAR) study was also summarized.
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
Huan-Huan
HH
Lu
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
Ping
P
Xue
School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430205, China. Electronic address: yyzhu531@163.com.
Yuan-Yuan
YY
Zhu
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
Xiu-Lian
XL
Ju
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
Xiao-Jiao
XJ
Zheng
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
Xun
X
Zhang
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
Ting
T
Xiao
KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium. Electronic address: christophe.pannecouque@kuleuven.be.
Christophe
C
Pannecouque
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
Ting-Ting
TT
Li
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China. Electronic address: shuangxigu@163.com.
Shuang-Xi
SX
Gu
D019380:Anti-HIV Agents / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D015497:HIV-1 / Q000187:drug effects*; D062105:Molecular Docking Simulation; D066244:Proton Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D019380:Anti-HIV Agents; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors
AIDS; Anti-HIV; Diarylpyrimidines; Nonnucleoside reverse transcriptase inhibitors; SAR