Synthesis and in vitro inhibitory activity on human platelet aggregation of novel properly substituted 4-(1-piperazinyl)coumarins.
Pursuing our chemical and biological studies in this field, we described the multistep preparation of the new 5-, 6-, or 7-alkoxy and 7-alkoxy-8-methyl substituted 4-(1-piperazinyl)coumarins 5d-v, as well as the in vitro evaluation of their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen or the Ca(2+) ionophore A23187. Compounds 5h-j,p,r-u showed notably high activity towards all the platelet aggregation inducers used, and the most active one, 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin (5t), proved to be a potent in vitro antiplatelet agent.
Di Braccio
Mario
M
Dipartimento di Scienze Farmaceutiche, Università di Genova, viale Benedetto XV, 16132 Genoa, Italy.
Grossi
Giancarlo
G
Roma
Giorgio
G
Grazia Signorello
Maria
M
Leoncini
Giuliana
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D015394:Molecular Structure; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*
D003374:Coumarins; D007476:Ionophores; D010975:Platelet Aggregation Inhibitors; D000001:Calcimycin; D000244:Adenosine Diphosphate; D003094:Collagen; D002118:Calcium