Antithrombic activity

Other 1,8-napht hyridines have demonstrated antithrombic activity (162)123 and tranquilizer, muscle relaxant, and hypnotic properties (163),124 as well as anticonvulsant behavior (163124 and 164125 ). Some other derivatives (165)... 

N- and C-substituted heptamethyleneimine exhibit antithrombic activity <90JAP(K)02II5I97>. 

Polymeric materials having antithrombogenic activity are very important and their development is expected in the field of artificial organs such as the artificial vessel or the devices for extracorporeal circulation. In previous papers >2 we described that the binding of sulfonate and amino acid sulfamide groups onto cross-linked polystyrene endows these materials with antithrombic activity which requires the presence of a plasma cofactor, antithrombin III. These insoluble materials operate as catalysts of the inactivation of thrombin by its inhibitor as does soluble heparin. The catalytic effect of this mucopolysaccharide was demonstrated to require the formation of complexes between heparin and either antithrombin III or thrombin or both > >. ... 

We now report results concerning the interactions between these two proteins and two of these polystyrene derivatives sulfonated polystyrene (PSSO3) and sulfonate-glutamic acid sulfonamide polystyrene (PSSO2GIU). The adsorption of each protein was studied either in purified system or in plasma and the binding constants were determined. Moreover, the catalysed formation of thrombin-anti-thrombin III complex was examined and compared with the antithrombic activity measured through thrombin clotting times of plasma preincubated with these polymers. 

The antithrombic activity of the polymers was first compared through the thrombin clotting times of platelet poor plasma (PPP) incubated with various amounts of suspended resin. The results were translated into the amount of inactivated thrombin as previously described and are reported in Fig. 4. These curves show that the inactivation of the same thrombin activity in plasma requires approximately 3 times more PSSO3 than PSSO2GIU. 

In previous papersl> the antithrombic activity of these polymers was demonstrated to involve one (or several) plasma cofactor as for instance antithrombin III. The catalytic effect of the polymers on the thrombin-AT reaction was evaluated by comparison of the TAT amounts generated during 10 seconds in presence or absence of polymer. In each case, the polymer suspension - or buffer - was first incubated with fresh platelet poor plasma. Then thrombin was introduced and after 10 seconds the reaction was blocked by addition of hirudin. The Fig. 5 shows a typical variation of TAT generation as a function of the amount of polymer present in the test. The TAT levels were measured in the supernatant bbtained by centrifugation of the final suspension and the results are expressed in percent of the maximum.of TAT complex which can be... 

Fig. 4. Antithrombic activity measured in plasma. PSSO2GIU O PSSO3 A. ...

Table 14 Composition, anticoagulant (antithrombic), and anticomplementary activities of dextran derivatives with different DS of carboxymethyl (CM), benzylamide (B) and sulfonate/sulfate (S) functions ...

Two other publications on the bioisosteric replacement of pyridine show similar results. The first paper reports the study of bioisosteric potential of diazines in the field of combined antithrombic thromboxane A2 synthetase inhibitors and receptor antagonists. On the basis of the structure-activity relationships (SAR) observed in this study, it turned out that only the 2-pyrazinyl, 4-pyridazinyl... 

The analog 21 of bisobrin, an antithrombic agent, has shown appreciable fibrinolytic activity in rats. ... 

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