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  • Towards dual antithrombotic compounds - Balancing thrombin inhibitory and fibrinogen GPIIb/IIIa binding inhibitory activities of 2,3-dihydro-1,4-benzodioxine derivatives through regio- and stereoisomerism
    Ilić, Miloš ...
    Enantiomers of 2,3-dihydro-1,4-benzodioxine derivatives possessing both thrombin and fibrinogen GPIIb/IIIa binding inhibitory activities were preparedfrom (R)- and (S)-glycidol as potential dual ... antithrombotic compounds.The influence of chirality and substitution pattern on thrombin inhibition and on inhibition of fibrinogen binding to GPIIb/IIIa was analyzed.Docking studies were used in an attempt to rationalize the results. The (S)-isomers of both 2,3-dihydro-1,4-benzodioxine regioisomers at positions 6 and 7 were found to be better thrombin inhibitors than the corresponding (R)-enantiomers, whereas we observed that stereochemistry does not display a consistent influence on fibrinogen GPIIb/ IIIa binding inhibitory activity. Compound 11b, the (S)-isomer of the 6-substituted regioisomer, possessed the best balanced dual activity, with Ki(thrombin) = 1.67 0.27 mM and IC50(GPIIb/IIIa) = 0.665 0.26 mM, raising the hope that merging anticoagulant and platelet antiaggregatory activities in the same molecule could lead to successful multitarget antithrombotic agents.
    Source: European journal of medicinal chemistry. - ISSN 0223-5234 (Vol. 62, April 2013, str. 329-340)
    Type of material - article, component part
    Publish date - 2013
    Language - english
    COBISS.SI-ID - 3391601

    Link(s):

    http://www.sciencedirect.com/science/article/pii/S022352341300010X#
    DOI

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