Structure-Based Design of 6-Chloro-4-aminoquinazoline-2-carboxamide Derivatives as Potent and Selective p21-Activated Kinase 4 (PAK4) Inhibitors was written by Hao, Chenzhou;Zhao, Fan;Song, Hongyan;Guo, Jing;Li, Xiaodong;Jiang, Xiaolin;Huan, Ran;Song, Shuai;Zhang, Qiaoling;Wang, Ruifeng;Wang, Kai;Pang, Yu;Liu, Tongchao;Lu, Tianqi;Huang, Wanxu;Wang, Jian;Lin, Bin;He, Zhonggui;Li, Haitao;Li, Feng;Zhao, Dongmei;Cheng, Maosheng. And the article was included in Journal of Medicinal Chemistry in 2018.COA of Formula: C11H22N2O2 This article mentions the following:
Herein, we report the discovery and characterization of a novel class of PAK4 inhibitors with a quinazoline scaffold. Based on the shape and chem. composition of the ATP-binding pocket of PAKs, we chose a 2,4-diaminoquinazoline series of inhibitors as a starting point. Guided by X-ray crystallog. and a structure-based drug design (SBDD) approach, a series of novel 4-aminoquinazoline-2-carboxamide PAK4 inhibitors were designed and synthesized. The inhibitors’ selectivity, therapeutic potency, and pharmaceutical properties were optimized. One of the best compounds, 31 (CZh226), showed remarkable PAK4 selectivity (346-fold vs PAK1) and favorable kinase selectivity profile. Moreover, this compound potently inhibited the migration and invasion of A549 tumor cells by regulating the PAK4-directed downstream signaling pathways in vitro. Taken together, these data support the further development of 31 as a lead compound for PAK4-targeted anticancer drug discovery and as a valuable research probe for the further biol. investigation of group II PAKs. In the experiment, the researchers used many compounds, for example, 1-Boc-2,6-dimethylpiperazine (cas: 688363-66-8COA of Formula: C11H22N2O2).
1-Boc-2,6-dimethylpiperazine (cas: 688363-66-8) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.COA of Formula: C11H22N2O2
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics