Design and Optimization of a Series of 1‑Sulfonyl­pyrazolo[4,3‑<i>b</i>]pyridines as Selective c‑Met Inhibitors Yuchi Ma Guangqiang Sun Danqi Chen Xia Peng Yue-Lei Chen Yi Su Yinchun Ji Jin Liang Xin Wang Lin Chen Jian Ding Bing Xiong Jing Ai Meiyu Geng Jingkang Shen 10.1021/jm502018y.s001 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 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 <b>7</b>. By rational design, a novel sulfonyl­pyrazolo­[4,3-<i>b</i>]­pyridine <b>9</b> 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 <b>46</b> was selected as a preclinical candidate for further anticancer drug development. 2015-03-12 00:00:00 series DMPK properties stability type sulfonyl candidate elaboration moietie Selective cancer cells pharmacokinetics studies 7. activation anticancer drug development Optimization potency Series basis vivo compound 46 interaction Sulfonyl inhibitor cancer therapy