Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1371900 | Bioorganic & Medicinal Chemistry Letters | 2009 | 4 Pages |
Abstract
A series of prolyl-N-isonicotinoyl-(L)-4-aminophenylalanine derivatives substituted at the proline 4-position with cyclic amines was evaluated as VLA-4 antagonists. The ring size and presence or absence of fluorine affected potency and receptor occupancy. The analog with 3,3-difluoropiperidine at the proline 4-position (13) was the most potent compound and had very good duration of receptor occupancy in vitro. The ethyl ester prodrug of 13 demonstrated excellent receptor occupancy after oral dosing in rats.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Shankar Venkatraman, Alec D. Lebsack, Kenneth Alves, Michael F. Gardner, Joyce James, Russell B. Lingham, Salony Maniar, Richard A. Mumford, Qian Si, Nicholas Stock, Kelly M. Treonze, Bowei Wang, Jasmine Zunic, Benito Munoz,