New Purines with Antiplatelet Activity

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).

New 1H‐Pyrazole‐4‐Carboxamides with Antiplatelet Activity

“…In a number of previous publications, we were able to show that the substitution of heterocycles rich in nitrogen like purines [1], indazoles [2], triazoles [3], oxadiazoles [4], imidazoles [5], pyrimidocinnolines [6], phthalazines [7], or thiazoles [8] with a carboxamide partial structure in addition to basic groups leads to a wide variety of compounds with antiplatelet activities in micromolar concentrations. In this paper, we wish to report a number of pyrazole derivatives fulfilling these structural requirements and, consequently, were promising to show remarkable antiplatelet activities.…”

Synthesis of 9-Acetoxyethyl-6-alkylamino-2-alkylthio Purines and Their Anti-platelet Aggregation Activity

“…2006 年 Rehse 等 [15] 制备了一系列的 2-酰胺基-6-取代 氨基-9-苄基嘌呤类化合物, 并对这些化合物进行了抑 制血小板凝聚活性的评价, 筛选出了一种对抑制 ADP 诱导的血小板凝集有显著效果的的化合物, 其 IC 50 ＝ 0.00045 μmol/L. 在 2011 年, 我们研究小组 [16,17] 分别报道了以鸟苷 为原料经羟基保护、重氮化、水解、O-烷基化和胺解反 应合成 2-烷氧基腺苷化合物和以腺嘌呤为原料合成 2-烷硫基腺嘌呤化合物, 同时测试了部分化合物的抗血小 板凝集活性, 得到了一个血小板最大凝集率仅为 6.15% 的 6-烷氨基腺苷化合物 [16] .…”