Discovery of Novel Indazoles as Potent and Selective PI3Kδ Inhibitors with High Efficacy for Treatment of Hepatocellular Carcinoma was written by Qi, Jifeng;Wang, Weihua;Tang, Yongmei;Lou, Shengying;Wang, Jiaer;Yuan, Tao;He, Qiaojun;Yang, Bo;Zhu, Hong;Cui, Sunliang. And the article was included in Journal of Medicinal Chemistry in 2022.Category: nitriles-buliding-blocks This article mentions the following:
A total of 26 indazole derivatives I (R1 = H, F, Cl, CF3; R2 = H, F, Me; R3 = Me, Et, isopropyl; R4 = pyridin-3-yl, 3,5-difluorophenyl, 4-cyanophenyl, etc.; R5 = 9H-purin-6-yl, 2-amino-9H-purin-6-yl, 3-cyanopyridin-2-yl, etc.) were designed and prepared to identify a novel compound I (R1 = Cl; R2 = H; R3 = methyl; R4 = pyridin-3-yl; R5 = 2,6-diamino-5-cyanopyrimidin-4-yl) (II) with good isoform selectivity, PK profile, and potency. Compared to Idelalisib and Sorafenib, the pharmacodynamic (PD) studies showed that II exhibits superior efficacy in HCC cell lines and xenograft models, and the mechanistic study showed that II robustly suppresses the downstream AKT pathway to induce subsequent apoptotic cell death in HCC models. Therefore, this work provides a new structural design of PI3Kδ inhibitors for a novel and efficient therapeutic small mol. toward HCC. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Category: nitriles-buliding-blocks).
4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. Nitrile function is a very important functional group because it can be manipulated to other functional groups such as carboxylic acid by hydrolysis or amine by reduction, respectively. Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine (RCH2NH2) or the tertiary amine ((RCH2)3N), depending on conditions.Category: nitriles-buliding-blocks
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts