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DOI: 10.1055/s-2004-822356
Dianhydrohexitole-Based Benzamidines: An Efficient Synthesis of New Factor Xa Inhibitors
Publication History
Publication Date:
03 May 2004 (online)
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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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Pd/C is preferred, since the use of Raney-nickel in MeOH-HOAc (see experimental part GP4 and GP5) leads to the formation of minor amounts of Ni(OAc)2, which is difficult to remove chromatographically.