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Issue 3, 2011
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Novel indolizine compounds as potent inhibitors of phosphodiesterase IV (PDE4): structure–activity relationship

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Abstract

A series of novel indolizine 2-oxoacetamides were designed and synthesized as PDE4 inhibitors. Preliminary SAR of this new class of compounds revealed key structural features required for high potency. Compounds 1ab and 2a are among the most potent inhibitors of PDE4 with low single nM IC50. Cellular activity was demonstrated by the inhibition of TNFα production from human PBMC with IC50 ranging from 14 to 72 nM. Docking analyses suggest the OH group in 1ab enhance the binding via an H-bond interaction with the PDE4 enzyme.

Graphical abstract: Novel indolizine compounds as potent inhibitors of phosphodiesterase IV (PDE4): structure–activity relationship

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Publication details

The article was received on 12 Nov 2010, accepted on 06 Dec 2010 and first published on 22 Dec 2010


Article type: Concise Article
DOI: 10.1039/C0MD00215A
Med. Chem. Commun., 2011,2, 176-180

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    Novel indolizine compounds as potent inhibitors of phosphodiesterase IV (PDE4): structure–activity relationship

    S. Chen, Z. Xia, M. Nagai, R. Lu, E. Kostik, T. Przewloka, M. Song, D. Chimmanamada, D. James, S. Zhang, J. Jiang, M. Ono, K. Koya and L. Sun, Med. Chem. Commun., 2011, 2, 176
    DOI: 10.1039/C0MD00215A

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