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ID: ALA1137970

Journal: Bioorg Med Chem Lett

Title: N,N-Dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines as potent factor Xa inhibitors.

Authors: Jia ZJ, Su T, Zuckett JF, Wu Y, Goldman EA, Li W, Zhang P, Clizbe LA, Song Y, Bauer SM, Huang W, Woolfrey J, Sinha U, Arfsten AE, Hutchaleelaha A, Hollenbach SJ, Lambing JL, Scarborough RM, Zhu BY.

Abstract: A class of N,N-dialkylated 4-(4-arylsulfonylpiperazine-1-carbonyl)-benzamidines and 4-((4-arylsulfonyl)-2-oxo-piperazin-1-ylmethyl)-benzamidines has been discovered as potent factor Xa inhibitors with desirable in vitro and in vivo anticoagulant activity, but with low oral bioavailability. The 5-chloroindole and 6-chlorobenzo[b]thiophene groups are optimal as the factor Xa S1 binding elements. The strategy of incorporating a side chain on the piperazine nucleus to enhance binding affinity has been examined.

CiteXplore: 15080981

DOI: 10.1016/j.bmcl.2004.02.049