Kim, Junwon Lee, Doohyun Park, Changmin So, Wonyoung Jo, Mina Ok, Taedong Kwon, Jeongjin Kong, Sunju Jo, Suyeon Kim, Youngmi Choi, Jihyun Kim, Hyoung Cheul Ko, Yoonae Choi, Inhee Park, Youngsam Yoon, Jaewan Ju, Moon Kyeong Kim, Junghwan Han, Sung-Jun Kim, Tae-Hee Cechetto, Jonathan Nam, Jiyoun Sommer, Peter Liuzzi, Michel Lee, Jinhwa No, Zaesung Discovery of Phenylaminopyridine Derivatives as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors We identified a novel class of aryl-substituted triazine compounds as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) during a high-throughput screening campaign that evaluated more than 200000 compounds for antihuman immunodeficiency virus (HIV) activity using a cell-based full replication assay. Herein, we disclose the optimization of the antiviral activity in a cell-based assay system leading to the discovery of compound <b>27</b>, which possessed excellent potency against wild-type HIV-1 (EC<sub>50</sub> = 0.2 nM) as well as viruses bearing Y181C and K103N resistance mutations in the reverse transcriptase gene. The X-ray crystal structure of compound <b>27</b> complexed with wild-type reverse transcriptase confirmed the mode of action of this novel class of NNRTIs. Introduction of a chloro functional group in the pyrazole moiety dramatically improved hERG and CYP inhibition profiles, yielding highly promising leads for further development. compound 27 complexed;antihuman immunodeficiency virus;NNRTI;transcriptase;assay;novel class;EC;K 103N resistance mutations;HIV;181C;CYP inhibition profiles 2012-08-09
    https://acs.figshare.com/articles/journal_contribution/Discovery_of_Phenylaminopyridine_Derivatives_as_Novel_HIV_1_Non_nucleoside_Reverse_Transcriptase_Inhibitors/2497720
10.1021/ml300146q.s001