Platelet aggregation inhibiting and anticoagulant effects of oligoamines, Part 33. From tetradecane- to octacosanediamines.
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.
Rehse
K
K
Institut für Pharmazie I der Freien Universität Berlin, Germany
Nolte-Driller
R
R
D000473:Alkanes / Q000737:chemistry*; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D003959:Diamines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009795:Octanes / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000188:drug therapy
D000473:Alkanes; D000925:Anticoagulants; D003959:Diamines; D009795:Octanes; D010975:Platelet Aggregation Inhibitors; C024713:n-tetradecane; C026728:octane