title: Synthesis and in vitro antiplatelet activity of new 4-(1-piperazinyl)coumarin derivatives. Human platelet phosphodiesterase 3 inhibitory properties of the two most effective compounds described and molecular modeling study on their interactions with phosphodiesterase 3A catalytic site.
abstract: The synthesis and in vitro antiplatelet activity significant data of coumarin derivatives 5i-x and quinolin-2(1H)-one derivatives 22a,b, as well as the corresponding structure-activity relationships are described. The recently reported 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin 5f and its potent 7-(2-morpholinoethoxy)-substituted new analogue 5u were notably more effective inhibitors of pure human platelet PDE3 than milrinone and cilostazol: these data were related, through a molecular modeling study, with the molecular interactions of the four compounds with the human PDE3A catalytic site.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV n. 3, I-16132 Genoa, Italy. roma@unige.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Roma
authors.forename: Mario
authors.initials: M
authors.lastname: Di Braccio
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Grossi
authors.forename: Daniela
authors.initials: D
authors.lastname: Piras
authors.forename: Giuliana
authors.initials: G
authors.lastname: Leoncini
authors.forename: Debora
authors.initials: D
authors.lastname: Bruzzese
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Signorello
authors.forename: Paola
authors.initials: P
authors.lastname: Fossa
authors.forename: Luisa
authors.initials: L
authors.lastname: Mosti
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000737:chemistry; D020134:Catalytic Domain; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C521969:8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin; C521970:8-methyl-7-(2-morpholinoethoxy)-4-(1-piperazinyl)-2H-1-benzopyran-2-one; D003374:Coumarins; D009025:Morpholines; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517287:PDE3A protein, human