title: New pyrimido[5,4-c]cinnolines with antiplatelet activities.
abstract: Twenty one new pyrimido[5,4-c]cinnolines containing different lipophilic moieties (viz. phenyl, 4-methoxyphenyl, 2-furanyl, 2-thienyl) in position 2 and additional basic groups (e.g., alkylaminopropyl, dialkylaminopropyl and cyclohexylaminopropyl) in position 4 of the title ring system have been prepared and investigated for antiplatelet effects (Born test). Ten of them inhibited the platelet aggregation induced by collagen with an IC(50) below 10 micromol/L (6a, 6b, 6c, 6g, 6h, 6i, 6k, 6m, 6q, 6u). A closer inspection of the antiplatelet effect with other inducers showed antagonism against adrenaline (6m), ADP antagonist (6i) and PAF antagonist activities (6m, 6i, 6u) in nanomolar (IC(50)) concentration ranges.
authors.affiliation: Institut für Pharmazie, Freie Universität Berlin, Germany. rehiwer@zedat.fu-berlin.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Rehse
authors.forename: Hedwig
authors.initials: H
authors.lastname: Gonska
mesh_terms: D001792:Blood Platelets / Q000187:drug effects; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D006574:Heterocyclic Compounds, 2-Ring; D010975:Platelet Aggregation Inhibitors; D003094:Collagen; C476282:cinnoline; D004837:Epinephrine