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.HPLC of Formula: 3034-41-1 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-Methyl-4-nitroimidazole (cas: 3034-41-1HPLC of Formula: 3034-41-1).
1-Methyl-4-nitroimidazole (cas: 3034-41-1) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. This ring system is present in important biological building blocks, such as histidine and the related hormone histamine.HPLC of Formula: 3034-41-1
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem