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  • Title: New purines with antiplatelet activity.
    Author: Märschenz K, Rehse K.
    Journal: Arch Pharm (Weinheim); 2006 Mar; 339(3):115-22. PubMed ID: 16493596.
    Abstract:
    Four purine-2,6-diamines, 4a, b, 5a, b, nineteen N-(purin-2-yl)benzenecarboxamides 6a-q, 7b, and one N-(purin-2-yl)-2-furanecarboxamide 8 were prepared for the first time and tested for their inhibition of blood platelet aggregation. Six compounds, 6a, b, h, m, o, p, inhibited the platelet aggregation induced by collagen with IC(50 )values between 3 and 10 micromol/L in the Born test. ADP, PAF, and adrenaline were used as specific aggregation inducers to examine the mechanism of the anti-aggregating activity. An astonishing pattern of activities in the nanomolar, with 6m, 7b, 8 and even subnanomolar range, with 6b, was observed. Compound 6b inhibited the platelet aggregation induced by ADP with an IC(50) = 0.45 nM (6m: 3.5 nM; 8: 30 nM). Compound 7b showed an antagonism against the inducer adrenaline with an IC(50) = 1.8 nM (6o: 20 nM; 8: 30 nM). The strongest antagonism against PAF was observed with 7b showing an IC(50) = 1 nM (6b: 35 nM; 8: 74 nM).
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