4.5 Article

Structure-based optimization of a potent class of arylamide FMS inhibitors

期刊

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 18, 期 12, 页码 3632-3637

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2008.04.059

关键词

FMS; cFMS; CSF-1R; M-CSF; colony-stimulating factor-1; macrophages; anti-inflammatory activity; idiosyncratic drug reactions

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An anti-inflammatory 1,2,4-phenylenetriamine-containing series of FMS inhibitors with a potential to form reactive metabolites was transformed into a series with equivalent potency by incorporation of carbon-based replacement groups. Structure-based modeling provided the framework to efficiently effect this transformation and restore potencies to previous levels. This optimization removed a risk factor for potential idiosyncratic drug reactions. (C) 2008 Elsevier Ltd. All rights reserved.

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