Synthesis and antiplatelet activity of 2-(diethylamino)-7-ethoxychromone and related compounds

Article abstract of DOI:10.1016/0223-5234(90)90187-8

2-(Diethylamino)-7-ethoxychromone 3a and its 2-(1-piperidinyl)analogue 3b were synthesized by reaction of 3-ethoxyphenol 1 with 3-(dialkylamino)-3-oxo-propanoic acid ethyl ester 2 in the presence of phosphorus oxychloride.With a view to improve their biological activity the above 7-ethoxychromones 3 were submitted to some structural modifications firstly involving the 4-CO group.The 4H-chromenes 4 and the 4-thiochromones 5 were obtained by action of suitable reagents.The compounds 5 were then easily transformed to 4-(methylthio)chromenylium iodides 6.Then from the 2-(diethylamino)-7-ethoxychromone 3a were obtained with suitable reactions the 3,6-diamino derivative 8, the 3- and 6-formyl derivatives 9a,b and the Mannich base 10.By action of acetic anhydride this latter compound yielded the methylenebis derivative 11.Most of the above compounds were tested in vitro for their inhibitory activities against human platelet aggregation induced by collagen, ADP and arachidonic acid.Among the tested compounds the 2-(diethylamino)-7-ethoxychromone 3a showed the highest activity.