376608-74-1Relevant articles and documents
Synthesis and biological evaluation of: N 6derivatives of 8-azapurine as novel antiplatelet agents
Tian, Nana,Wang, Juan,Wang, Yeming,Yan, Hong,Zhao, Zhichang
, p. 1414 - 1427 (2021/11/09)
Two series of novel N6 derivatives of 8-azapurine I and II were designed as antiplatelet agents. Series I and II were N6 amino derivatives and N6 hydrazone derivatives of 8-azapurine, respectively. The compounds were synthesized in acceptable yields via conventional procedures, including nucleophilic substitution, diazotization, and amination or hydrazonation with amino alcohol and 4,6-dichloropyrimidine as starting materials. To assess the ability of the synthesized compounds as antiplatelet agents, the ADP-induced platelet aggregation assay of Born was performed both in vitro and in vivo using ticagrelor as a reference control substance. The analysis of the structure-activity relationship and molecular docking were also discussed in detail. The results demonstrated that series I and II compounds exhibited antiplatelet activity in vitro and IIh was the most active compound (IC50 = 0.20 μM) among the target compounds, being almost 4-fold better than ticagrelor (IC50 = 0.74 μM). For a preliminary assessment of the safety profile, a bleeding test (mouse tail) and a single-dose toxicity test were conducted. The use of compound IIh resulted in a shorter bleeding time, less blood loss and lower acute toxicity compared to ticagrelor. In addition, a molecular docking study was performed to investigate the binding capacity and binding mode between IIh and P2Y12. This journal is
Preparation process of ticagrelor intermediate
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Paragraph 0014; 0024; 0025; 0029; 0030, (2020/12/09)
The invention discloses a preparation process of a ticagrelor intermediate. The process comprises the following steps of dissolving 4,6-dichloro-2-(propylthio)-5-aminopyrimidine and sodium bicarbonatein water at a temperature of 15-25 DEG C; performing heating, adding an aqueous solution of 2-[[(3aR, 4S, 6R, 6aS)-6-amino-2, 2-dimethyltetrahydro-3aH- cyclopentadiene [d] [1,3]-dioxol-4-yl] oxy]-1-ethanol (III) or a salt thereof, and performing stirring at a constant temperature until a reaction is finished; stopping heating, cooling a reaction mixture, adding ethyl acetate, separating liquid, and washing an organic phase with water; stirring the organic phase, slowly dropwise adding n-hexane at a certain temperature, and separating out a solid to obtain the intermediate. According to the process, the use of excessive organic base such as triethylamine is avoided, the cheap and easily available sodium bicarbonate is used, the production cost is low, the reaction time is short, three wastes are few, and the obtained ticagrelor intermediate is the solid with the high purity, is high in yield and is more suitable for industrial production.
Production process of ticagrelor fine product
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Paragraph 0020-0022; 0027-0029; 0034-0036, (2020/12/09)
The present invention discloses a production process of a ticagrelor fine product. The process comprises the steps of adopting 4,6-dichloro-5-amino-2-propylthiopyrimidine (IIa) and a compound (IIb) asstarting raw materials, and carrying out five processes including a substitution process I, a cyclization process, a substitution process II, a hydrolysis process and a refining process to finally obtain the ticagrelor fine product. The method provides a ticagrelor production process, uses cheap and easily available raw materials, has the advantages of low production cost, simple reaction conditions, convenient post-treatment, high yield and high product purity, and is more suitable for industrial production.
