GL 522-Y-1 appears to be an effective anticoagulant and an antithrombotic substance with direct mode of action and effectiveness after oral administration.On the basis of its unique antithrombotic properties, GL 522-Y-1 seems to open a new pathway in the field of antithrombotics.This prompted investigations with its derivativesThe aim of the modifications of the GL 522-Y-1 mol. was to increase the therapeutic index of GL 522-Y-1 and to increase its bioavailability.GL 522-Y-1 has been derivatized into simple salts, ethers, and acylates.In this study we investigated the effects of one of the GL 522-Y-1 derivative, GL 2021 on thrombosis in vivo after i.v. as well as oral application, and on hemostasis in vitro.In contrast to GL 522-Y-1, its Me ether, GL 2O21 exhibits weaker antithrombotic activity after i.v. injection and virtually no effect after oral application in our animal model of thrombosis.It demonstrates also weaker than GL 522-Y-1 anticoagulant activity in vitro.GL 2021 possesses a lower polyanionic charge than GL 522-Y-1, which is believed to be necessary for the hemostatic activity.It is not clear whether the charge or the structure of the mol. is responsible for the inhibition of thrombin.Concluding, polysulfonate derivatives are relatively mild antithrombotic agents.Furthermore, due to toxicity, their development has been stopped.
