title: Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold.
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).
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia.
authors.forename: Miloš
authors.initials: M
authors.lastname: Ilić
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
authors.forename: Janez
authors.initials: J
authors.lastname: Ilaš
mesh_terms: D048588:Benzoxazines / Q000737:chemistry*; D054879:Halogenation; D006490:Hemostatics / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D048588:Benzoxazines; D006490:Hemostatics; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013917:Thrombin