Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 20, Issue 15, Pages 4479-4482Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2010.06.037
Keywords
Proinflammatory cytokine; TNF-alpha; Anti-TNF-alpha agent; SA13353; Urea; 2,4-Dinitrobenzenesulfonamide; Manual synthesizer
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A three substituted urea derivative, SA13353 (compound 1a), exhibited potent inhibitory activity against lipopolysaccharide (LPS)-induced TNF-alpha production. We focused on the 1,1-substituted moiety (R(1) and R(2)) of SA13353 and investigated substituent effects of this moiety on LPS-induced TNF-alpha production by oral administration in rats. The synthesis of the urea derivatives was performed rapidly in a one-pot manner using a manual synthesizer. Several compounds containing hydrophobic substituents at this moiety showed more potent inhibitory activities than SA13353. (C) 2010 Elsevier Ltd. All rights reserved.
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