TY - DATA T1 - Design and Optimization of a Series of 1‑Sulfonyl­pyrazolo[4,3‑b]pyridines as Selective c‑Met Inhibitors PY - 2015/03/12 AU - Yuchi Ma AU - Guangqiang Sun AU - Danqi Chen AU - Xia Peng AU - Yue-Lei Chen AU - Yi Su AU - Yinchun Ji AU - Jin Liang AU - Xin Wang AU - Lin Chen AU - Jian Ding AU - Bing Xiong AU - Jing Ai AU - Meiyu Geng AU - Jingkang Shen UR - https://acs.figshare.com/articles/journal_contribution/Design_and_Optimization_of_a_Series_of_1_Sulfonyl_pyrazolo_4_3_i_b_i_pyridines_as_Selective_c_Met_Inhibitors/2186710 DO - 10.1021/jm502018y.s001 L4 - https://ndownloader.figshare.com/files/3820876 KW - series KW - DMPK properties KW - stability KW - type KW - sulfonyl KW - candidate KW - elaboration KW - moietie KW - Selective KW - cancer cells KW - pharmacokinetics studies KW - 7. KW - activation KW - anticancer drug development KW - Optimization KW - potency KW - Series KW - basis KW - vivo KW - compound 46 KW - interaction KW - Sulfonyl KW - inhibitor KW - cancer therapy N2 - c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonyl­pyrazolo­[4,3-b]­pyridine 9 with improved DMPK properties was discovered. Further elaboration of π–π stacking interactions and solvent accessible polar moieties led to a series of highly potent and selective type I c-Met inhibitors. On the basis of in vitro and in vivo pharmacological and pharmacokinetics studies, compound 46 was selected as a preclinical candidate for further anticancer drug development. ER -