New series of 6-substituted coumarin derivatives as effective factor Xa inhibitors : synthesis, in vivo antithrombotic evaluation and molecular docking
Copyright © 2013 Elsevier Inc. All rights reserved..
Despite recent progress in antithrombotic therapy, there's still an unmet medical need for safe and orally available anticoagulants. Encouraged by the marked antithrombotic and anticoagulant activities of some coumarin derivatives, twenty-three new N-coumarinyl-4-amidinobenzamides 4a-f and 6-heterocycle substituted coumarin derivatives 5, 6a,b, 10a-e, 12a-e and 14a-d were synthesized and evaluated for their in vivo antithrombotic activity. The most active congeners were the unsubstituted amidine 4a (36.5 s), coumarinyl oxadiazole 5 (42.3 s), bis coumarinyl oxadiazole 6b (37.8 s) and coumarinyl pyrazole 10b (38.5 s) that presented prothrombin time (PT) values comparable to the reference drug warfarin (42.3 s). Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the coagulation factor Xa (FXa) binding site.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
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| Enthalten in: |
Bioorganic chemistry - 52(2014) vom: 28. Feb., Seite 31-43 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Amin, Kamelia M [VerfasserIn] |
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| Links: |
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| Themen: |
5Q7ZVV76EI |
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| Anmerkungen: |
Date Completed 15.08.2014 Date Revised 20.11.2014 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2013.11.002 |
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| funding: |
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| 520 | |a Copyright © 2013 Elsevier Inc. All rights reserved. | ||
| 520 | |a Despite recent progress in antithrombotic therapy, there's still an unmet medical need for safe and orally available anticoagulants. Encouraged by the marked antithrombotic and anticoagulant activities of some coumarin derivatives, twenty-three new N-coumarinyl-4-amidinobenzamides 4a-f and 6-heterocycle substituted coumarin derivatives 5, 6a,b, 10a-e, 12a-e and 14a-d were synthesized and evaluated for their in vivo antithrombotic activity. The most active congeners were the unsubstituted amidine 4a (36.5 s), coumarinyl oxadiazole 5 (42.3 s), bis coumarinyl oxadiazole 6b (37.8 s) and coumarinyl pyrazole 10b (38.5 s) that presented prothrombin time (PT) values comparable to the reference drug warfarin (42.3 s). Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the coagulation factor Xa (FXa) binding site | ||
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