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• W1900240057 abstract "Human α-thrombin is a particularly promising target for anticoagulant therapy, and identification of oral small-molecular inhibitors of thrombin remains a research focus. On the basis of the X-ray crystal structure of human α-thrombin and its inhibitor dabigatran, we designed and synthesized a series of dabigatran etexilate mimics containing a novel tricyclic fused scaffold. The biological evaluations reveal that all of the compounds possess moderate activity of antiplatelet aggregation induced by thrombin in vitro. Moreover, compound I-8, which contains 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP), a cleavable moiety with antiplatelet activity, shows the best anticoagulant effect among the tested compounds in vivo. Those synthesized compounds that have better in vitro activity were subjected to bleeding complication tests, and the results demonstrate that the novel compounds are less likely to have bleeding risk than dabigatran etexilate." @default.
• W1900240057 created "2016-06-24" @default.
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• W1900240057 date "2015-06-29" @default.
• W1900240057 modified "2023-10-09" @default.
• W1900240057 title "Design, Synthesis, and Biological Evaluation of Dabigatran Etexilate Mimics, a Novel Class of Thrombin Inhibitors" @default.
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• W1900240057 doi "https://doi.org/10.1002/ardp.201500101" @default.
• W1900240057 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26120827" @default.
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