Synthesis and biological evaluation of N 6 derivatives of 8-azapurine as novel antiplatelet agents
This journal is © The Royal Society of Chemistry..
Two series of novel N 6 derivatives of 8-azapurine I and II were designed as antiplatelet agents. Series I and II were N 6 amino derivatives and N 6 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
RSC medicinal chemistry - 12(2021), 8 vom: 18. Aug., Seite 1414-1427 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Zhichang [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Revised 03.04.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1039/d1md00128k |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM330015524 |
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| 520 | |a This journal is © The Royal Society of Chemistry. | ||
| 520 | |a Two series of novel N 6 derivatives of 8-azapurine I and II were designed as antiplatelet agents. Series I and II were N 6 amino derivatives and N 6 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 | ||
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| 700 | 1 | |a Wang, Juan |e verfasserin |4 aut | |
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