Several non-salt and solid thienopyridine derivatives as oral P2Y12 receptor inhibitors with good stability

Bioorganic & Medicinal Chemistry Letters
2022.0

Abstract

A series of novel thienopyridine derivatives were designed and synthesized as P2Y<sub>12</sub> receptor inhibitors. Several solid compounds were assessed for inhibitory effect where they exhibited stronger potency than clopidogrel. Compound 6b and 6g were evaluated for metabolism to verify that they could overcome clopidogrel resistance and for toxicity where they showed lower toxicity than prasugrel. Compound 6b exhibited lower risk of bleeding than prasugrel and showed good stability under stress testing. Overall, as a promising antiplatelet agent, representative compound 6b showed the following advantages: (1) no drug resistance for CYP2C19 poor metabolizers; (2) higher potency than clopidogrel; (3) lower toxicity than prasugrel; (4) lower risk of bleeding than prasugrel; (5) good stability as a non-salt solid.

Knowledge Graph

Similar Paper

Several non-salt and solid thienopyridine derivatives as oral P2Y12 receptor inhibitors with good stability
Bioorganic &amp; Medicinal Chemistry Letters 2022.0
Thieno[2,3-b]pyridine derivatives are potent anti-platelet drugs, inhibiting platelet activation, aggregation and showing synergy with aspirin
European Journal of Medicinal Chemistry 2018.0
Overcoming Clopidogrel Resistance: Discovery of Vicagrel as a Highly Potent and Orally Bioavailable Antiplatelet Agent
Journal of Medicinal Chemistry 2012.0
Optimization of P2Y<sub>12</sub> 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
Journal of Medicinal Chemistry 2019.0
Lead Optimization of Ethyl 6-Aminonicotinate Acyl Sulfonamides as Antagonists of the P2Y<sub>12</sub> Receptor. Separation of the Antithrombotic Effect and Bleeding for Candidate Drug AZD1283
Journal of Medicinal Chemistry 2013.0
Identification of 1-{2-[4-chloro-1′-(2,2-dimethylpropyl)-7-hydroxy-1,2-dihydrospiro[indole-3,4′-piperidine]-1-yl]phenyl}-3-{5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl}urea, a potent, efficacious and orally bioavailable P2Y1 antagonist as an antiplatelet agent
Bioorganic &amp; Medicinal Chemistry Letters 2014.0
Tetrahydrothienopyridine derivatives as novel GPIIb/IIIa antagonists
Bioorganic &amp; Medicinal Chemistry Letters 1996.0
P2Y12 antagonists: Approved drugs, potential naturally isolated and synthesised compounds, and related in-silico studies
European Journal of Medicinal Chemistry 2022.0
Designing analogs of ticlopidine, a wall teichoic acid inhibitor, to avoid formation of its oxidative metabolites
Bioorganic &amp; Medicinal Chemistry Letters 2014.0
Novel Arylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-Dioxides as Inhibitors of Platelet Aggregation. 1. Synthesis and Pharmacological Evaluation
Journal of Medicinal Chemistry 1999.0