New pyrimido[5,4-c]cinnolines with antiplatelet activities.
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.
Rehse
Klaus
K
Institut für Pharmazie, Freie Universität Berlin, Germany. rehiwer@zedat.fu-berlin.de
Gonska
Hedwig
H
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
D006574:Heterocyclic Compounds, 2-Ring; D010975:Platelet Aggregation Inhibitors; D003094:Collagen; C476282:cinnoline; D004837:Epinephrine