| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1372111 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
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.
Graphical abstractCompounds such as 5j (IC50 = 0.11 nM) are potent inhibitors of VLA-4.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
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Authors
Thomas S. Reger, Jasmine Zunic, Nicholas Stock, Bowei Wang, Nicholas D. Smith, Benito Munoz, Mitchell D. Green, Michael F. Gardner, Joyce P. James, Weichao Chen, Kenneth Alves, Qian Si, Kelly M. Treonze, Russell B. Lingham, Richard A. Mumford,