Synthesis and characterization of non-steroidal ligands for the glucocorticoid receptor: selective quinoline derivatives with prednisolone-equivalent functional activity.
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Coghlan MJ, Kym PR, Elmore SW, Wang AX, Luly JR, Wilcox D, Stashko M, Lin CW, Miner J, Tyree C, Nakane M, Jacobson P, Lane BC
Synthesis and characterization of non-steroidal ligands for the glucocorticoid receptor: selective quinoline derivatives with prednisolone-equivalent functional activity.
J Med Chem. 2001 Aug 30;44(18):2879-85.
- PubMed ID
- 11520196 [ View in PubMed]
- Abstract
A novel class of functional ligands for the human glucocorticoid receptor is described. Substituents in the C-10 position of the tetracyclic core are essential for glucocorticoid receptor (GR) selectivity versus other steroid receptors. The C-5 position is derivatized with meta-substituted aromatic groups, resulting in analogues with a high affinity for GR (K(i) = 2.4-9.3 nM) and functional activity comparable to prednisolone in reporter gene assays of glucocorticoid-mediated gene transcription. The biological activity of these novel quinolines was also prednisolone-equivalent in whole cell assays of glucocorticoid function, and compound 13 was similar to prednisolone (po ED(50) = 2.8 mpk for 13 vs ED(50) = 1.2 mpk for prednisolone) in a rodent model of asthma (sephadex-induced eosinophil influx).
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Prednisolone Glucocorticoid receptor IC 50 (nM) 41 N/A N/A Details Prednisolone Glucocorticoid receptor Ki (nM) 2.4 N/A N/A Details Prednisolone Glucocorticoid receptor IC 50 (nM) 2.1 N/A N/A Details Prednisolone Glucocorticoid receptor IC 50 (nM) 8 N/A N/A Details Prednisolone Glucocorticoid receptor IC 50 (nM) 3.8 N/A N/A Details