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Bioorg Med Chem Lett. 2010 Feb 1;20(3):1173-6. doi: 10.1016/j.bmcl.2009.12.009. Epub 2009 Dec 4.

Heterocycle-substituted proline dipeptides as potent VLA-4 antagonists.

Author information

1
Department of Medicinal Chemistry, Merck Research Laboratories, San Diego, CA 92121, USA. thomas_reger@merck.com

Abstract

A variety of N-linked tertiary amines and heteroarylamines were examined at the 4-position of sulfonylated proline dipeptides in order to improve VLA-4 receptor off-rates and overcome the issue of CYP3A4 time-dependent inhibition of ester prodrugs. A tight-binding inhibitor 5j with a long off-rate provided sustained receptor occupancy despite poor oral pharmacokinetics.

PMID:
20022493
DOI:
10.1016/j.bmcl.2009.12.009
[Indexed for MEDLINE]

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