摘要：

As a further part of our chemical and biological studies in this field, we describe the multistep preparations of the properly substituted 2-(1-piperazinyl)chromone , 4-(1-piperazinyl)coumarins –, their linear benzo-fused analogues , and ,, bicyclic (–) and tricyclic (,) fused derivatives of 6-(1-piperazinyl)pyrimidin-4(3)-one, and of the 4-pyrido[1,2-]pyrimidine derivatives ,. The in vitro evaluation of their inhibitory properties towards human platelet aggregation induced in platelet-rich plasma by ADP, collagen, or the Ca ionophore A23187 showed the high activity of compounds – and ,,, among which the coumarins and proved to be, in that order, the most effective in vitro antiplatelet agents until now synthesized by us. Thus, in order to consider also the 4-aminocoumarin structural class, we developed a new statistically significant 3-D QSAR model, more general than the one previously obtained, through a further CoMFA study based on the antiplatelet activity data and molecular steric and electrostatic potentials of both the previously studied and herein described compounds.Several title compounds were synthesized and evaluated in vitro for their inhibitory properties on human platelet aggregation. Among them, the substituted 4-(1-piperazinyl)coumarin displayed the highest activity: IC (μM) 1.9±0.2 (ADP, 5.0 μM), 1.8±0.4 (collagen, 5.0 μg/mL), 1.1±0.2 (A23187, 20.0 μM). Structure–antiplatelet activity relationship studies of the previously and now described compounds led to the development of a statistically robust CoMFA model showing at the 3-D level the main interactions modulating the biological activity.

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