244768-53-4Relevant articles and documents
Scaffold hopping in discovery of HIV-1 non-nucleoside reverse transcriptase inhibitors: From CH(CN)-DABOs to CH(CN)-dapys
Chen, Fen-Er,Li, Ting-Ting,Pannecouque, Christophe,Zhuang, Chun-Lin,de Clercq, Erik
, (2020/04/10)
Scaffold hopping is a frequently-used strategy in the development of non-nucleoside reverse transcriptase inhibitors. Herein, CH(CN)-DAPYs were designed by hopping the cyano-methylene linker of our previous published CH(CN)-DABOs onto the etravirine (ETR). Eighteen CH(CN)-DAPYs were synthesized and evaluated for their anti-HIV activity. Most compounds exhibited promising activity against wild-type (WT) HIV-1. Compounds B4 (EC50 = 6 nM) and B6 (EC50 = 8 nM) showed single-digit nanomolar potency against WT HIV-1. Moreover, these two compounds had EC50 values of 0.06 and 0.08 μM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 μM). The preliminary structure-activity relationship (SAR) indicated that introducing substitutions on C2 of the 4-cyanophenyl group could improve antiviral activity. Molecular docking predicted that the cyano-methylene linker was positioned into the hydrophobic cavity formed by Y181/Y188 and V179 residues.
Synthesis and biological evaluation of CHX-DAPYs as HIV-1 non-nucleoside reverse transcriptase inhibitors
Yan, Zi-Hong,Wu, Hai-Qiu,Chen, Wen-Xue,Wu, Yan,Piao, Hu-Ri,He, Qiu-Qin,Chen, Fen-Er,De Clercq, Erik,Pannecouque, Christophe
, p. 3220 - 3226 (2014/06/09)
A series of new diarylpyrimidines (DAPYs) characterized by a halogen atom on the methylene linker between wing I and the central pyrimidine ring was synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. The two most promising compou
Lead optimization of diarylpyrimidines as non-nucleoside inhibitors of HIV-1 reverse transcriptase
Zeng, Zhao-Sen,Liang, Yong-Hong,Feng, Xiao-Qing,Chen, Fen-Er,Pannecouque, Christophe,Balzarini, Jan,De Clercq, Erik
scheme or table, p. 837 - 840 (2011/02/24)
Antiviral agents: A series of CN-CH2-DAPY analogues were identified as novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) against HIV-1. Most of the newly synthesized compounds exhibited strong activity against wild-type HIV-1.
