Differentiation of in vitro transcriptional repression and activation profiles of selective glucocorticoid modulators

The SAR at C-5 of the 10-methoxy-2,2,4-trimethylbenzopyrano[3,4-f]quinoline core leading to identification of (−) anti 1-methylcyclohexen-3-yl as the optimum substituent that imparts minimal GR mediated in vitro transcriptional activation while maintaining full transcriptional repression is described. The in vitro profile of these candidates in human cell assays relevant to the therapeutic window of glucocorticoid modulators is outlined. The SAR at C-5 of the 10-methoxy-2,2,4-trimethylbenzopyrano[3,4-f]quinoline core leading to identification of (−) anti 1-methylcyclohexen-3-yl as the optimum substituent that imparts minimal GR mediated in vitro transcriptional activation while maintaining full transcriptional repression is described. The in vitro profile of these candidates in human cell assays relevant to the therapeutic window of glucocorticoid modulators is outlined.