Nonsteroidal dissociated glucocorticoid agonists containing azaindoles as steroid A-ring mimetics.

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Riether D, Harcken C, Razavi H, Kuzmich D, Gilmore T, Bentzien J, Pack EJ, Souza D, Nelson RM, Kukulka A, Fadra TN, Zuvela-Jelaska L, Pelletier J, Dinallo R, Panzenbeck M, Torcellini C, Nabozny GH, Thomson DS

Nonsteroidal dissociated glucocorticoid agonists containing azaindoles as steroid A-ring mimetics.

J Med Chem. 2010 Sep 23;53(18):6681-98. doi: 10.1021/jm100751q.

PubMed ID
20735001 [ View in PubMed
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Abstract

Syntheses and structure-activity relationships (SAR) of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain azaindole moieties as A-ring mimetics and display various degrees of in vitro dissociation between gene transrepression and transactivation. Collagen induced arthritis studies in mouse have demonstrated that in vitro dissociated compounds (R)-16 and (R)-37 have steroid-like anti-inflammatory properties with improved metabolic side effect profiles, such as a reduced increase in body fat and serum insulin levels, compared to steroids.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DexamethasoneGlucocorticoid receptorIC 50 (nM)3.4N/AN/ADetails
DexamethasoneGlucocorticoid receptorIC 50 (nM)0.51N/AN/ADetails
PrednisoloneGlucocorticoid receptorIC 50 (nM)15N/AN/ADetails
PrednisoloneGlucocorticoid receptorIC 50 (nM)6.6N/AN/ADetails