title: Design and synthesis of novel platelet fibrinogen receptor antagonists with 2H-1,4-benzoxazine-3(4H)-one scaffold. A systematic study.
abstract: New platelet glycoprotein IIb/IIIa (GP IIb/IIIa, integrin alpha(IIb)beta3) antagonists were prepared on a 2H-1,4-benzoxazine-3(4H)-one scaffold. Their anti-aggregatory activities in human platelet rich plasma and their affinity towards alpha(IIb)beta3 and alpha(V)beta3 integrins were assessed. Various substitution positions and side chain variations were studied. In contrast to the generally accepted model, compounds containing ethyl esters as aspartate mimetics were in general more active than the corresponding free acids. We suggest an explanation for the observed behaviour of these new compounds.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
authors.forename: Marko
authors.initials: M
authors.lastname: Anderluh
authors.forename: Jozko
authors.initials: J
authors.lastname: Cesar
authors.forename: Petra
authors.initials: P
authors.lastname: Stefanic
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
authors.forename: Damjan
authors.initials: D
authors.lastname: Janes
authors.forename: Jernej
authors.initials: J
authors.lastname: Murn
authors.forename: Kristina
authors.initials: K
authors.lastname: Nadrah
authors.forename: Mojca
authors.initials: M
authors.lastname: Tominc
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Addicks
authors.forename: Athanassios
authors.initials: A
authors.lastname: Giannis
authors.forename: Mojca
authors.initials: M
authors.lastname: Stegnar
authors.forename: Marija Sollner
authors.initials: MS
authors.lastname: Dolenc
mesh_terms: D001224:Aspartic Acid; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects*; D015195:Drug Design; D039302:Integrin alphaVbeta3; D018716:Molecular Mimicry; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D039341:Receptors, Fibrinogen / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D048588:Benzoxazines; D039302:Integrin alphaVbeta3; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D039341:Receptors, Fibrinogen; D001224:Aspartic Acid