Die Titelverbindungen des Typs (IV) werden durch Reaktion der Pyrazole (I) bzw. des Dimeren (II) mit Hydrazinen des Typs (III) synthetisiert.

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Anticoagulants usually have no antiplatelet effect and platelet function inhibitors do not interact with the coagulation factors. Since thrombin has a decisive role in thrombus formation (growth and stabilization), inhibitors of the effect of thrombin on platelets may be of special importance in developing a novel type of anticoagulant with antiplatelet properties.D-Phe-Pro-Arg-H /I/ designed and synthetized in our Institute was found to be a highly specific,reversible non-competitive inhibitorgOf thrombin,a specific platelet agonist. (K.= 1x10-8 M). /I/ was administered parenterally and orally to white New Zealand rabbits and to beagle dogs. The kinetics of action was recorded by measuring the WBCT, APTT, PT, TT,platelet count (PC) and platelet aggregation (PA). Optimum degree of anticoagulation was considered by the values proposed by Verstraete and Verwilghen. /I/ was shown to be a highly specific inhibitor of PA induced by thrombin.No direct interaction between the inhibitor and the platelet membrane could be detected. Aggregability of human platelets in citrated PRP and that of the gel-filtrated platelets induced by ADP or collagen did not change after incubation with /I/. The antiplatelet effect of /I/ was studied by ex vivo experiments where the inhibitor was the anticoagulant ( 30 ug/ml whole blood ) instead of citrate. Comparing the aggregability caused by several inducers in citrated human PRP with that of in /I/-PRP a significant difference was observed when epinephrine was the PA-inducer. /I/ acts via formation of an enzyme-inhibitor complex that inhibits the binding of thrombin on their receptor-sites at the platelet membrane. In vivo experiments showed a close correlation between TT and PA induced by thrombin. /I/ proved completely harmless to platelets and red blood cells. No significant change in PC could be detected.

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