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Synthesis of heparin-like antithrombotics having perphosphorylated thrombin binding domains

Bioorganic & Medicinal Chemistry, ISSN: 0968-0896, Vol: 7, Issue: 9, Page: 1881-1890
1999
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The synthesis of three heparin analogues (i.e. compounds VI–VIII Figure 1 Scheme 4(i) DMF, H2O, 1h; (ii) 0.1 M aqueous Na2HPO4 (pH 7.0), 0.05 M NH2OH, 2h (26a→VI, 68%), (26b→VII, 80%), (27→VIII, 51%). ) having perphosphorylated thrombin binding domains (TBDs) is reported. These compounds were tested in vitro for their antithrombin III (ATIII)-mediated anti-Xa and antithrombin activities. Conjugates VI and VIII show a remarkable increase in antithrombin activity compared to the structurally related conjugates with persulfated TBDs (i.e. compounds IV and V ), whereas compound VII displays a diminished activity.

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