Optimization of P2Y12 Antagonist Ethyl 6-(4-((Benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283) Led to the Discovery of an Oral Antiplatelet Agent with Improved Druglike Properties was written by Kong, Deyu;Xue, Tao;Guo, Bin;Cheng, Jianjun;Liu, Shunyin;Wei, Jianhai;Lu, Zhengyu;Liu, Haoran;Gong, Guoqing;Lan, Tian;Hu, Wenhao;Yang, Yushe. And the article was included in Journal of Medicinal Chemistry in 2019.Application of 638-07-3 The following contents are mentioned in the article:
P2Y12 antagonists are widely used as antiplatelet agents for the prevention and treatment of arterial thrombosis. Based on the scaffold of a known P2Y12 antagonist AZD1283 (I), a series of novel bicyclic pyridine derivatives were designed and synthesized. The cyclization of the ester substituent on the pyridine ring to the ortho-Me group led to lactone analogs of AZD1283 that showed significantly enhanced metabolic stability in subsequent structure-pharmacokinetic relationship studies. The metabolic stability was further enhanced by adding a 4-Me substituent to the piperidinyl moiety. Compound II displayed potent inhibition of platelet aggregation in vitro as well as antithrombotic efficacy in a rat ferric chloride model. Moreover, II showed a safety profile that was superior to what was observed for clopidogrel in a rat tail-bleeding model. These results support the further evaluation of compound II as a promising drug candidate. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Application of 638-07-3).
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. Alkyl chlorides readily react with amines to give substituted amines. Alkyl chlorides are substituted by softer halides such as the iodide in the Finkelstein reaction.Application of 638-07-3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics