Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XXI: 4,4′‐Alkylene‐bis‐sydnone Imines

Martens

1993

One mesoionic 4,4'-propylene-bis-oxazol-5-imine (5), two 2,2'-m-phenylene-bis-imidazol-4-imines (9a,b), five 4,4'-benzene-bis-(and tris)-thiazol-2-amines (13a,b, 14a-c) and 14 3,3'-benzene-bis-(and tris)-1,2,4-thiadiazolimines (18a-o) were synthesized and assayed for their antiplatelet and anticoagulant activities. The most potent compound was the tris-thiadiazole derivative 18m which inhibited the aggregation of platelets induced by collagen at a concentration of 10 mumol/L by 50 percent (Born-test). No anticoagulant effects (Quick-test) were observed up to 400 mumol/L. In the thiazolamine series combined antiplatelet and anticoagulant activities were seen.

Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XXII: Bisoxazol‐, Bisimidazol‐, Bisthiazol‐ and Oligo‐1,2,4‐thiadiazolimines

Martens

1993

Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XXIV: Interactions between Oligosydnone Imines and Albumine or Phospholipids

Piechocki

1994

Oligosydnone imines are strongly bound to albumin (alpha < 1%) in pure water. In saline, however, this effect is abolished (alpha approximately 80%). 4,4'-Propylene-bis-3-hexyl-sydnone-5-imine hydrochloride (1) moderately binds to phosphatidylcholine liposomes (PC, alpha approximately 34%). This is increased by phosphatidylethanolamine (PE). In PC/PE vesicles alpha is about 7%. The binding is further enhanced by the incorporation of negatively charged phospholipids (PL) like phosphatidylserine (PS). In PC/PE/PS liposomes complete binding of 1 can be achieved. This holds especially true if the composition of the liposomes is similar to the PL composition of platelet membranes. The results suggest that the antiplatelet activity of 1 is mediated by the bindings to negatively charged PL in the platelet membrane.

Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, Part 33 From Tetradecane‐ to Octacosanediamines

Nolte‐Driller

1996

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.