Search

Your search keyword '"Liu, Shunyin"' showing total 4 results
Start Over Author "Liu, Shunyin"
4 results on '"Liu, Shunyin"'

1. 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

Author

Kong, Deyu, primary, Xue, Tao, additional, Guo, Bin, additional, Cheng, Jianjun, additional, Liu, Shunyin, additional, Wei, Jianhai, additional, Lu, Zhengyu, additional, Liu, Haoran, additional, Gong, Guoqing, additional, Lan, Tian, additional, Hu, Wenhao, additional, and Yang, Yushe, additional

Published
2019
Full Text
View/download PDF

3. Optimization of P2Y12Antagonist 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

Author

Kong, Deyu, Xue, Tao, Guo, Bin, Cheng, Jianjun, Liu, Shunyin, Wei, Jianhai, Lu, Zhengyu, Liu, Haoran, Gong, Guoqing, Lan, Tian, Hu, Wenhao, and Yang, Yushe

Abstract

P2Y12antagonists are widely used as antiplatelet agents for the prevention and treatment of arterial thrombosis. Based on the scaffold of a known P2Y12antagonist AZD1283, a series of novel bicyclic pyridine derivatives were designed and synthesized. The cyclization of the ester substituent on the pyridine ring to the ortho-methyl group led to lactone analogues of AZD1283 that showed significantly enhanced metabolic stability in subsequent structure–pharmacokinetic relationship studies. The metabolic stability was further enhanced by adding a 4-methyl substituent to the piperidinyl moiety. Compound 58ldisplayed potent inhibition of platelet aggregation in vitro as well as antithrombotic efficacy in a rat ferric chloride model. Moreover, 58lshowed 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 58las a promising drug candidate.

Published
2019
Full Text
View/download PDF

4. Optimization of P2Y 12 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.

Author

Kong D, Xue T, Guo B, Cheng J, Liu S, Wei J, Lu Z, Liu H, Gong G, Lan T, Hu W, and Yang Y

Subjects
Animals, Humans, Male, Niacin chemistry, Niacin pharmacokinetics, Niacin pharmacology, Platelet Aggregation Inhibitors chemistry, Platelet Aggregation Inhibitors pharmacokinetics, Purinergic P2Y Receptor Antagonists chemistry, Purinergic P2Y Receptor Antagonists pharmacokinetics, Rats, Rats, Sprague-Dawley, Rats, Wistar, Structure-Activity Relationship, Sulfonamides chemistry, Sulfonamides pharmacokinetics, Drug Discovery, Niacin analogs & derivatives, Platelet Aggregation Inhibitors pharmacology, Purinergic P2Y Receptor Antagonists pharmacology, Receptors, Purinergic P2Y12 drug effects, Sulfonamides pharmacology
Abstract

P2Y 12 antagonists are widely used as antiplatelet agents for the prevention and treatment of arterial thrombosis. Based on the scaffold of a known P2Y 12 antagonist AZD1283, a series of novel bicyclic pyridine derivatives were designed and synthesized. The cyclization of the ester substituent on the pyridine ring to the ortho-methyl group led to lactone analogues of AZD1283 that showed significantly enhanced metabolic stability in subsequent structure-pharmacokinetic relationship studies. The metabolic stability was further enhanced by adding a 4-methyl substituent to the piperidinyl moiety. Compound 58l displayed potent inhibition of platelet aggregation in vitro as well as antithrombotic efficacy in a rat ferric chloride model. Moreover, 58l 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 58l as a promising drug candidate.

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results