1224740-91-3Relevant articles and documents
Discovery of phenylaminopyridine derivatives as novel HIV-1 non-nucleoside reverse transcriptase inhibitors
Kim, Junwon,Park, Changmin,So, Wonyoung,Jo, Mina,Ok, Taedong,Kwon, Jeongjin,Jo, Suyeon,Choi, Jihyun,Kim, Hyoung Cheul,Lee, Doohyun,Kim, Youngmi,Ko, Yoonae,Choi, Inhee,Kong, Sunju,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
, p. 678 - 682,5 (2012)
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 27, which possessed excellent potency against wild-type HIV-1 (EC50 = 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 27 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.