Synthesis and Evaluation of 1-Arylsulfonyl-3-piperazinone Derivatives as Factor Xa Inhibitor

概要

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Intravascular clot formation is an important factor in a number of cardiovascular diseases. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa(FXa), which is a key enzyme in coagulation cascade responsible for the generation of thrombin by limited proteolysis of its zymogen, prothrombin. We have investigated 1-arylsulfonyl-3-piperazinone derivatives, containing a 4-(piperidino)pyridine group in place of guanidino and/or amidino groups, and discovered compound M55113(30a: 4-[(6-Chloro-2-naphthalenyl)sulfonyl]-1-[[1-(4-pyridinyl)-4-piperidinyl]-methyl]piperazinone), as a potent inhibitor of FXa(IC_<50>=0.06μM)with high selectivity for FXa over trypsin and thrombin.
公益社団法人日本薬学会の論文
2001-10-01