Dianhydrohexitole-Based Benzamidines: An Efficient Synthesis of New Factor Xa Inhibitors

Marko Vogler; Ulrich Koert; Klaus Harms; Dieter Dorsch; Johannes Gleitz; Peter Raddatz

doi:10.1055/s-2004-822356

PAPER

Dianhydrohexitole-Based Benzamidines: An Efficient Synthesis of New Factor Xa Inhibitors

Marko Vogler^a, Ulrich Koert*^a, Klaus Harms^a, Dieter Dorsch^b, Johannes Gleitz^b, Peter Raddatz^b
^a Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany
Fax: Fax:+49(6421)2825677; e-Mail: E-mail: koert@chemie.uni-marburg.de;
^b Merck KGaA, Preclinical Research & Development, 64271 Darmstadt, Germany

Abstract

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Abstract

Dianhydrohexitole-based benzamidines were synthesised as potential factor Xa inhibitors. The key steps for the synthesis of a bis-benzamidine series were nucleophilic aromatic substitutions and Mitsunobu reactions to introduce substituted phenyl ether moieties. Mono-benzamidines with an ortho-substituted biphenyl group were prepared using a Negishi-type cross coupling procedure. The benzamidines showed high biological activity and selectivity for factor Xa inhibition.

Key words

isosorbide - amidines - Mitsunobu reaction - cross-coupling - drugs - factor Xa inhibitors

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References

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