New antithrombotic 1‐Phthalazinamines with Serotonin Antagonistic Properties

Abstract We report nineteen 4‐aryl‐ and 4‐arylalkyl‐1‐phthalazinamines ( 5 — 8 ) which we prepared and tested for antithrombotic properties. All compounds were assayed for their antiplatelet activity in the “Born test” with collagen as inducer of the aggregation. N ‐[4‐(1 H ‐1, 2, 4‐triazol‐1‐yl)butyl]‐4‐phenyl‐1‐phthalazin‐amine ( 7 c ) was the most potent compound, having an IC 50 of 8 μM. When 5‐HT (Serotonin) was used to start aggregation the N ‐(furan‐2‐yl‐methyl)‐4‐phenyl‐1‐pthtalazinamine ( 8 a ) had an IC 50 of 2 μM. In vivo potencies were highly significant. N ‐[5‐(1 H ‐1, 2, 4‐triazol‐1‐yl)pentyl]‐4‐phenyl‐1‐phthalazinamine ( 7 d ) inhibited thrombus formation by 12% (P < 0.002) in arterioles and 7% (P < 0.01) in venoles as tested with our laser thrombosis model. For compound 8 a we surprisingly found an antagonism to the 5HT 2A receptor, which is most likely the mechanism of the inhibition of aggregation by this compound.