Synthesis and Inhibitory Activity on Platelet Aggregation of 13′-Aza and Other ω-Chain Modified BW245C Analogues
作者:Paur Barraclough、Michael Brockwell、A. Gordon Caldwell、Derek A. Demaine、C. John Harris、W. Richard King、Ray J. Stepney、Clifford J. Wharton、Brendan J. R. Whittle
DOI:10.1002/ardp.19943270508
日期:——
BW245C analogues which have 15′‐keto, ‐oximino, ‐sulphinyl, ‐sulphonyl, ‐methyl, ‐1‐adamantyl, 14′‐hydroxy, 16′‐hydroxy, 13′‐14′‐NHCH,‐ NH‐CH2, or ‐NH‐CO groups have been synthesized and evaluated for their activity in inhibiting platelet aggregation and for their cardiovascular actions: the 13′‐aza analogues 13 and 14 are more potent inhibitors of human platelet aggregation than BW245C (0.3, 0.6
BW245C 类似物,具有 15'-酮基、-肟基、-亚磺酰基、-磺酰基、-甲基、-1-金刚烷基、14'-羟基、16'-羟基、13'-14'-NHCH、-NH , 或 -NH -CO 基团已被合成并评估其抑制血小板聚集和心血管作用的活性:13' - 氮杂类似物 13 和 14 是比 BW245C 更有效的人血小板聚集抑制剂(0.3、0.6 和 0.2 xPGl2)和这些对血小板聚集的抑制活性在体外孵育时增加。更详细地研究了 13 (BW68C) 和 14 (BW361C) 的前列腺素模拟特性,发现它们的血小板抑制和血管舒张作用比 BW245C 的持续时间更长。对 BW245C ω - 链的所有其他修饰都导致了效力较低或无活性的化合物。