Rehse K, Nolte-Driller R
Institut für Pharmazie I der Freien Universität Berlin, Germany
Arch Pharm (Weinheim). 1996 Apr;329(4):191-6. doi: 10.1002/ardp.19963290404.
Twenty alkanediamines were designed according to structure-activity relationships drawn from previous parts of this series and synthesized. Their general structure is CH3-(CH2)n-CHNH2-(CH2)m-CHNH2-(CH2)n-CH3, (n = 2-10; m = 3-6). Twelve of them inhibited the aggregation of human blood platelets in concentrations between 3-10 micromol/L halfmaximally (Born test, inducer collagen). With increasing m a decreasing n is necessary to achieve the optimum activity. In the most active compounds (7b, 7e, 7p) it is found that m + n = 9. When the nitrogen functions are hydroxyalkylated secondary amines with similar antiplatelet effects are obtained. The conversion of the amino groups into syndronimines is accompanied by the loss of activity. The bisethoxycarbonylderivatives of 7f and 7m (8f, 8m) exhibited antithrombotic effects in rats after oral administration.
根据本系列前文得出的构效关系设计并合成了20种链烷二胺。它们的一般结构为CH3-(CH2)n-CHNH2-(CH2)m-CHNH2-(CH2)n-CH3，（n = 2 - 10；m = 3 - 6）。其中12种在3 - 10微摩尔/升浓度下对人血小板聚集有半数最大抑制作用（博恩试验，诱导剂为胶原蛋白）。为达到最佳活性，随着m的增加，n需减小。在活性最高的化合物（7b、7e、7p）中发现m + n = 9。当氮官能团为羟烷基化仲胺时，可获得类似的抗血小板作用。氨基转化为辛德龙胺会导致活性丧失。7f和7m的双乙氧基羰基衍生物（8f、8m）经口服给药后在大鼠中表现出抗血栓作用。
