Discovery of a Pyrimidinedione Derivative as a Potent and Orally Bioavailable Axl Inhibitor was written by Zhang, Hefeng;Peng, Xia;Dai, Yang;Shao, Jingwei;Ji, Yinchun;Sun, Yiming;Liu, Bo;Cheng, Xu;Ai, Jing;Duan, Wenhu. And the article was included in Journal of Medicinal Chemistry in 2021.Recommanded Product: Ethyl 4-chloro-3-oxobutanoate The following contents are mentioned in the article:
The receptor tyrosine kinase Axl plays important roles in promoting cancer progression, metastasis, and drug resistance and has been identified as a promising target for anticancer therapeutics. We used mol. modeling-assisted structural optimization starting with the low micromolar potency compound I to discover compound II, a highly potent and orally bioavailable Axl inhibitor. Selectivity profiling showed that II could inhibit the well-known oncogenic kinase Met with equal potency to its inhibition of Axl superfamily kinases. Compound II significantly inhibited cellular Axl and Met signaling, suppressed Axl- and Met-driven cell proliferation, and restrained Gas6/Axl-mediated cancer cell migration or invasion. Furthermore, II exhibited significant antitumor efficacy in Axl-driven and Met-driven tumor xenograft models, causing tumor stasis or regression at well-tolerated doses. All these favorable data make II a promising therapeutic candidate for cancer treatment. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Recommanded Product: Ethyl 4-chloro-3-oxobutanoate).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Recommanded Product: Ethyl 4-chloro-3-oxobutanoate
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics