Synthesis of Dianhydrohexitole-based Benzamidines as Factor Xa Inhibitors Using Cross Couplings, Phenyl Ether and Amidine Formations as Key Steps

Abstract Starting with isosorbide or isomannide several dianhydrohexitole-based benzamidines were synthesized as potential factor Xa inhibitors. The key steps for the synthesis of the bisbenzamidines were nucleophilic aromatic substitutions and Mitsunobu reactions to build up phenylethers. Another t...

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Bibliographic Details
Published in:Synlett 2003-09, Vol.2003 (11), p.1683-1687
Main Authors: Vogler, Marko, Koert, Ulrich, Dorsch, Dieter, Gleitz, Johannes, Raddatz, Peter
Format: Article
Language:English
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Summary:Abstract Starting with isosorbide or isomannide several dianhydrohexitole-based benzamidines were synthesized as potential factor Xa inhibitors. The key steps for the synthesis of the bisbenzamidines were nucleophilic aromatic substitutions and Mitsunobu reactions to build up phenylethers. Another type of monobenzamidines had ORTHO-substituted biphenyl groups. Their synthesis necessitated an optimization of cross coupling procedures due to the great sterical hindrance of the ORTHO-substituent. The benz­amidines showed biological activity against factor Xa and selectivity against other serine proteases.
ISSN:0936-5214
1437-2096
DOI:10.1055/s-2003-41426