Synthesis and Evaluation of 1-ArylsuIfonyl-3-piperazinone Derivatives as Factor Xa Inhibitors~(1-4))V.A Series of New Derivatives Containing a Spiro[imidazo[1,2-a]pyrazine-2(3H),4'-piperidin]-5(1H)-one Scaffold

摘要

We have already reported unique compounds containing a N,O-spiro acetal structure as an orally active factor Xa(FXa)inhibitor.This time,we described a N,N-spiro acetal structure as an analogue of the N,O-spiro acetal structure for an orally active FXa inhibitor.The synthesis of these analogues could be achieved in a similar fashion to the N,O-spiro acetal synthesis.Consequently,FXa inhibitory activity was increased and more active compounds could be found(M58163:IC_(50)=0.61 nM,M58169:IC_(50)=0.58 nM).Additionally,the absolute configuration could be determined by X-ray crystallography analysis(M58169:(R)-config.).