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Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold
Miloš Ilić1, Danijel Kikelj, Janez Ilaš
1University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia.
Abstract:
Fluorinated 3,4-dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa receptor antagonistic activities were prepared as potential dual antithrombotic compounds. Fluorine scan (3-fluorobenzyl, 4-fluorobenzyl, 3,4-difluorobenzyl and 3,5-difluorobenzyl substituted compounds) was performed in order to obtain 6-(carboxymethyl)(3,4-difluorobenzyl)amino compound (9i) as the most potent compound with balanced dual activity (K(i(Thr))=0.33±0.07μM, IC(50(GP IIb/IIIa))=1.1±0.6μM).
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