Nonsteroidal selective glucocorticoid modulators: the effect of C-5 alkyl substitution on the transcriptional activation/repression profile of 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines.

摘要: The preparation and characterization of a series selective glucocorticoid receptor modulators are described. preliminary structure−activity relationship nonaromatic C-5 substitution on the tetracyclic quinoline core showed preference for small lipophilic side chains. Proper at this position maintained transcriptional repression proinflammatory transcription factors while diminishing activation activity ligand/glucocorticoid complex. optimal compounds described in study were allyl analogue 18 cyclopentyl 32. These candidates slightly less potent, highly efficacious E-selectin with significantly reduced levels response element reporter gene assays vs prednisolone. Allyl was evaluated vivo. An oral dose an ED50 = 1.7 mg/kg as compared to 1.2 prednisolone Sephadex-induced pulmonary eosinophilia model 15 ...