The Development of New Low-Molecular-Weight Factor Xa Inhibitors that are Potential Anticoagulants
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Despite the introduction of direct oral anticoagulants, the search for new oral anticoagulants remains an urgent task.
OBJECTIVE: By using docking and scoring, based on physical methods, simple chemical rules, methods of synthesis, and activity measurement, develop new low-molecular-weight inhibitors of factor Xa, which are potential anticoagulants.
METHODS: The development of leads was based on chemical synthesis and structure-based drug design methods. The basic idea was to combine the two approaches: one based on predictive modeling and the other based on the experimental data.
RESULTS: In this study, we developed some nanomolar leads. Further chemical modification improved the inhibition constant by more than one order.
DISCUSSION: The method proposed in this paper, as well as other methods, includes virtual screening, chemical synthesis, and activity measurement. However, the most time-consuming process in this method (chemical synthesis) was simplified, and the cost was reduced to the extent that was allowed; a very simple chemical reaction was chosen, i.e., the formation of an amide bond.
CONCLUSION: In this work, we demonstrated how using simple chemical rules based on the structurebased drug design, substances with a nanomolar concentration of activity can be developed.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Current drug discovery technologies - 19(2022), 1 vom: 23., Seite e010921191770 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tovbin, Dmitry G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.05.2022 Date Revised 06.06.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1568009621666210224104940 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM322133289 |
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| 245 | 1 | 4 | |a The Development of New Low-Molecular-Weight Factor Xa Inhibitors that are Potential Anticoagulants |
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| 500 | |a Date Revised 06.06.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Despite the introduction of direct oral anticoagulants, the search for new oral anticoagulants remains an urgent task | ||
| 520 | |a OBJECTIVE: By using docking and scoring, based on physical methods, simple chemical rules, methods of synthesis, and activity measurement, develop new low-molecular-weight inhibitors of factor Xa, which are potential anticoagulants | ||
| 520 | |a METHODS: The development of leads was based on chemical synthesis and structure-based drug design methods. The basic idea was to combine the two approaches: one based on predictive modeling and the other based on the experimental data | ||
| 520 | |a RESULTS: In this study, we developed some nanomolar leads. Further chemical modification improved the inhibition constant by more than one order | ||
| 520 | |a DISCUSSION: The method proposed in this paper, as well as other methods, includes virtual screening, chemical synthesis, and activity measurement. However, the most time-consuming process in this method (chemical synthesis) was simplified, and the cost was reduced to the extent that was allowed; a very simple chemical reaction was chosen, i.e., the formation of an amide bond | ||
| 520 | |a CONCLUSION: In this work, we demonstrated how using simple chemical rules based on the structurebased drug design, substances with a nanomolar concentration of activity can be developed | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Chemical amide synthesis | |
| 650 | 4 | |a Factor Xa (FXa) | |
| 650 | 4 | |a antithrombotic agents | |
| 650 | 4 | |a antithrombotic drug | |
| 650 | 4 | |a direct oral anticoagulant | |
| 650 | 4 | |a drug design methods | |
| 650 | 7 | |a Amides |2 NLM | |
| 650 | 7 | |a Anticoagulants |2 NLM | |
| 650 | 7 | |a Factor Xa Inhibitors |2 NLM | |
| 700 | 1 | |a Tarasov, Dmitry N |e verfasserin |4 aut | |
| 700 | 1 | |a Malakhov, Dmitry V |e verfasserin |4 aut | |
| 700 | 1 | |a Tserkovnikova, Natalia A |e verfasserin |4 aut | |
| 700 | 1 | |a Aybush, Arseniy V |e verfasserin |4 aut | |
| 700 | 1 | |a Drozd, Natalia N |e verfasserin |4 aut | |
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