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Highly Potent, Orally Available Anti-inflammatory Broad-Spectrum Chemokine Inhibitors

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posted on 11.06.2009, 00:00 authored by David J. Fox, Jill Reckless, Hannah Lingard, Stuart Warren, David J. Grainger
A series of 3-acylaminocaprolactams are inhibitors of chemokine-induced chemotaxis. Branching of the side chain α-carbon provides highly potent inhibitors of a range of CC and CXC chemokines. The most potent compound has an ED50 of 40 pM. Selected compounds were tested in an in vivo inflammatory assay, and the best compound reduces TNF-α levels with an ED50 of 0.1 μg/kg when administered by either subcutaneous injection or oral delivery.