Discovery of novel dihydro-9,10-ethano-anthracene carboxamides as glucocorticoid receptor modulators.

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Yang BV, Vaccaro W, Doweyko AM, Doweyko LM, Huynh T, Tortolani D, Nadler SG, McKay L, Somerville J, Holloway DA, Habte S, Weinstein DS, Barrish JC

Discovery of novel dihydro-9,10-ethano-anthracene carboxamides as glucocorticoid receptor modulators.

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2139-43. doi: 10.1016/j.bmcl.2009.03.006. Epub 2009 Mar 9.

PubMed ID
19321341 [ View in PubMed
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Abstract

A series of dihydro-9,10-ethano-anthracene-11-carboxamides as novel glucocorticoid receptor modulators is reported. SAR exploration identified compounds from this series displaying a promising dissociation profile in discriminating between transrepression and transactivation activities. 17a is a partial agonist of GR-mediated transactivation which elicits potent and efficacious transrepression in reporter gene assays. A hypothetical binding mode is provided which accounts for the induction of functional activity by a bridgehead methyl group.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DexamethasoneGlucocorticoid receptorKi (nM)1.1N/AN/ADetails
DexamethasoneGlucocorticoid receptorEC 50 (nM)2.5N/AN/ADetails
DexamethasoneGlucocorticoid receptorEC 50 (nM)1.1N/AN/ADetails
DexamethasoneGlucocorticoid receptorEC 50 (nM)4.2N/AN/ADetails
PrednisoloneGlucocorticoid receptorKi (nM)1.5N/AN/ADetails
PrednisoloneGlucocorticoid receptorEC 50 (nM)15.8N/AN/ADetails
PrednisoloneGlucocorticoid receptorEC 50 (nM)13.6N/AN/ADetails
PrednisoloneGlucocorticoid receptorEC 50 (nM)82.7N/AN/ADetails