The design and synthesis of novel alpha-ketoamide-based p38 MAP kinase inhibitors.

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Montalban AG, Boman E, Chang CD, Ceide SC, Dahl R, Dalesandro D, Delaet NG, Erb E, Ernst JT, Gibbs A, Kahl J, Kessler L, Lundstrom J, Miller S, Nakanishi H, Roberts E, Saiah E, Sullivan R, Wang Z, Larson CJ

The design and synthesis of novel alpha-ketoamide-based p38 MAP kinase inhibitors.

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1772-7. doi: 10.1016/j.bmcl.2008.02.033. Epub 2008 Feb 16.

PubMed ID
18325768 [ View in PubMed
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Abstract

We have identified a novel series of potent p38 MAP kinase inhibitors through structure-based design which due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME and in vivo PK studies show these compounds to have drug-like characteristics which could result in the development of an oral treatment for inflammatory conditions.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DoramapimodMitogen-activated protein kinase 14IC 50 (nM)44N/AN/ADetails
DoramapimodMitogen-activated protein kinase 14IC 50 (nM)17N/AN/ADetails
NeflamapimodMitogen-activated protein kinase 14IC 50 (nM)29N/AN/ADetails
NeflamapimodMitogen-activated protein kinase 14IC 50 (nM)5300N/AN/ADetails