A. Balbi

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

Abstract 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.