Discovery of a potent series of non-steroidal non alpha-trifluoromethyl carbinol glucocorticoid receptor agonists with reduced lipophilicity.

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Diallo H, Angell DC, Barnett HA, Biggadike K, Coe DM, Cooper TW, Craven A, Gray JR, House D, Jack TI, Keeling SP, Macdonald SJ, McLay IM, Oliver S, Taylor SJ, Uings IJ, Wellaway N

Discovery of a potent series of non-steroidal non alpha-trifluoromethyl carbinol glucocorticoid receptor agonists with reduced lipophilicity.

Bioorg Med Chem Lett. 2011 Feb 15;21(4):1126-33. doi: 10.1016/j.bmcl.2010.12.121. Epub 2010 Dec 31.

PubMed ID
21257309 [ View in PubMed
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Abstract

A novel series of indazole non-steroidal glucocorticoid receptor agonist has been discovered. This series features a sulfonamide central core and meta amides which interact with the extended ligand binding domain. This series has produced some of the most potent and least lipophilic agonists of which we are aware such as 20a (NFkappaB pIC(50) 8.3 (100%), clogP 1.9). Certain analogues in this series also display evidence for modulated pharmacology.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DexamethasoneGlucocorticoid receptorIC 50 (nM)1N/AN/ADetails
DexamethasoneGlucocorticoid receptorIC 50 (nM)12.59N/AN/ADetails
DexamethasoneGlucocorticoid receptorIC 50 (nM)3.98N/AN/ADetails