Hou, Shaohua; Yang, Xiping; Yang, Yuejing; Tong, Yu; Chen, Quanwei; Wan, Boheng; Wei, Ran; Lu, Tao; Chen, Yadong; Hu, Qinghua published the artcile< Design, synthesis and biological evaluation of 1H-indazole derivatives as novel ASK1 inhibitors>, COA of Formula: C11H16BNO2, the main research area is aryl indazole preparation ASK inhibition mol docking SAR; 1H-indazole derivatives; ASK1 inhibitor; Inflammatory bowel disease.
A series of novel ASK1 inhibitors, e.g., I and II with 1H-indazole scaffold were designed, synthesized and evaluated for their ASK1 kinase activity and AP1-HEK293 cell inhibitory effect. Systematic structure-activity relationship (SAR) efforts led to the discovery of promising compound II, which showed excellent in vitro ASK1 kinase activity and potent inhibitory effects on ASK1 in AP1-HEK293 cells. In a tumor necrosis factor-α (TNF-α)-induced HT-29 intestinal epithelial cell model, compound II exhibited a significantly protective effect on cell viability comparable to that of GS-4997; moreover, compound II exhibited no obvious cytotoxicity against HT-29 cells at concentrations up to 25μM. Mechanistic research demonstrated that compound II suppressed phosphorylation in the ASK1-p38/JNK signaling pathway in HT-29 cells and regulated the expression levels of apoptosis-related proteins. Altogether, these results showed that compound II may serve as a potential candidate compound for the treatment of inflammatory bowel disease (IBD).
European Journal of Medicinal Chemistry published new progress about Amides Role: PAC (Pharmacological Activity), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 329214-79-1 belongs to class pyridine-derivatives, and the molecular formula is C11H16BNO2, COA of Formula: C11H16BNO2.