title: Synthesis, in vitro antiplatelet activity and molecular modelling studies of 10-substituted 2-(1-piperazinyl)pyrimido[1,2-a]benzimidazol-4(10H)-ones.
abstract: The multistep preparation of the new 10-substituted 2-(1-piperazinyl)pyrimido[1,2-a]benzimidazol-4(10H)-ones 6a-o, and of the two isomers 10-ethyl-2-(diethylamino)pyrimido[1,2-a]benzimidazol-4(10H)-one 6p and 10-ethyl-4-(diethylamino)pyrimido[1,2-a]benzimidazol-2(10H)-one 13, 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 were here described. Nine out of fifteen 2-(1-piperazinyl)derivatives (6g-o) showed good inhibitory properties towards all the platelet aggregation agonists used. Moreover, a molecular modelling study has been performed on two of the best compounds of this series (6i and 6o) to confirm in silico their interactions with the catalytic site of human platelet PDE3, using the X-ray data of the PDE3B isoform in complex with an inhibitor.
authors: Dipartimento di Farmacia, Sezione Chimica Farmaceutica, Università di Genova, Viale Benedetto XV, 16132 Genoa, Italy. dbraccio@unige.it
authors: Mario
authors: M
authors: Di Braccio
authors: Giancarlo
authors: G
authors: Grossi
authors: Maria Grazia
authors: MG
authors: Signorello
authors: Giuliana
authors: G
authors: Leoncini
authors: Elena
authors: E
authors: Cichero
authors: Paola
authors: P
authors: Fossa
authors: Silvana
authors: S
authors: Alfei
authors: Gianluca
authors: G
authors: Damonte
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012016:Reference Values; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D010975:Platelet Aggregation Inhibitors; D011744:Pyrimidinones