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Synthesis 2002(14): 2023-2036
DOI: 10.1055/s-2002-34389
PAPER
© Georg Thieme Verlag Stuttgart · New York

Aromatic β-Amino Acids as Asp-Phg Mimics in LDV Derived VLA-4 Antagonists­

Volkmar Wehner*a, Horst Blumb, Michael Kurza, Hans Ulrich Stilza
a Chemistry, Aventis Pharma Deutschland GmbH, 65926 Frankfurt am Main, Germany
Fax: +490(69)331399; e-Mail: volkmar.wehner@aventis.com;
b DG Thrombotic/Degenerative Joint Diseases, Aventis Pharma Deutschland GmbH, 65926 Frankfurt am Main, Germany
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Publikationsverlauf

Received 28 June 2002
Publikationsdatum:
26. September 2002 (online)

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Abstract

Aromatic β-amino acid esters 2a-h were prepared in racemic and enantiomerically pure form by the Radionow reaction or based on the method described by Davis and used as mimics of the Asp-Phg C-terminus in LDV derived VLA-4 antagonists. As a promising β-amino acid ester, 11 was identified and used for the synthesis of the highly potent VLA-4 antagonist S9059 with an IC50 of 1.6 nM in a cell attachment assay.

Key words

amino acids - esters - asymmetric synthesis - chiral auxiliaries - VLA-4 antagonists

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