Conformationally restricted quinazolone derivatives as PI3Kδ-selective inhibitors: the design, synthesis and biological evaluation was written by Ma, Xiaodong;Fang, Fang;Tao, Qiangqiang;Shen, Li;Zhong, Guochen;Qiao, Tao;Lv, Xiaoqing;Li, Jiaming. And the article was included in MedChemComm in 2019.Reference of 60025-09-4 This article mentions the following:
A series of structurally novel quinazolone-based PI3Kδ-selective inhibitors were designed and synthesized via the approach of conformational restriction. The majority of them exhibited two-digit to single-digit nanomolar IC50 values against PI3Kδ, along with low micromolar to submicromolar GI50 values against human malignant B-cell line SU-DHL-6. The representative compound, with the most potent PI3Kd inhibitory activity (IC50 = 6.3 nM) and anti-proliferative activity (GI50 = 0.21 μM) in this series, was further evaluated for its PI3Kδ selectivity, capability to down-regulate PI3K signaling in SU-DHL-6 cells, in vitro metabolic stability, and pharmacokinetic (PK) properties. The exptl. results illustrated that this compound, as a promising lead, merits extensive structural optimization for exploring novel PI3Kδ-selective inhibitors as clin. candidates. In the experiment, the researchers used many compounds, for example, 4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4Reference of 60025-09-4).
4-Amino-6-chloropyrimidine-5-carbonitrile (cas: 60025-09-4) belongs to nitriles. There has been no report on the microbial biosynthesis of nitriles and the physiological function of such enzymes, nor was it not even known whether aliphatic and aromatic nitriles are biological compounds or just petrochemicals. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.Reference of 60025-09-4
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts