1,2-FUSED PYRIMIDINES .7. 3-(DIALKYLAMINO)-1H-PYRIMIDO[1,2-A]QUINOLIN-1-ONES AND 2-(DIALKYLAMINO)-4H-PYRIMIDO[2,1-A]ISOQUINOLIN-4-ONES AS ANTIPLATELET COMPOUNDS

A number of 3-(dialkylamino)-1H-pyrimido[1,2-a]quinolin-1 ones 3 and 2-(dialkylamino)-4H-pyrimido [2,1-a]isoquinolin-4-ones 4 were prepared by treating the corresponding chloro derivatives with an excess of dialkylamines. The highest in vitro antiplatelet activity was obtained when the dialkylamino substituent was 1-piperazinyl (compounds 3g and 4e). The novel 2-(1-piperazinyl)-4H-pyrido[ ,2-a]pyrimidin-4-one 2a was also prepared by an analogous procedure, which resulted in the most active compound towards all the platelet aggregation inducers used (ADP, collagen, A 23187). Moreover, some examples of 1-(dialkylamino)-3H pyrimido[l,2-a]quinolin-3-ones 5 and 4-(dialkylamino)-2H-pyrimido[2,1-a]isoquinolin-2-ones 6 were also obtained (together with negligible or lower amounts of the corresponding isomers 3 and 4, respectively) from the cyclocondensation of the appropriate ethyl N,N-dialkylmalonamate/phosphorus oxychloride reagents 13 with 2-aminoquinoline or 1-aminoisoquinoline. These;latter compounds showed a rather low antiplatelet activity.