title: Differentiation of in vitro transcriptional repression and activation profiles of selective glucocorticoid modulators.
abstract: 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.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-3500, USA. steve.elmore@abbott.com
authors.forename: Steven W
authors.initials: SW
authors.lastname: Elmore
authors.forename: John K
authors.initials: JK
authors.lastname: Pratt
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Coghlan
authors.forename: Yue
authors.initials: Y
authors.lastname: Mao
authors.forename: Brian E
authors.initials: BE
authors.lastname: Green
authors.forename: David D
authors.initials: DD
authors.lastname: Anderson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Stashko
authors.forename: Chun W
authors.initials: CW
authors.lastname: Lin
authors.forename: Douglas
authors.initials: D
authors.lastname: Falls
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakane
authors.forename: Loan
authors.initials: L
authors.lastname: Miller
authors.forename: Curtis M
authors.initials: CM
authors.lastname: Tyree
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Miner
authors.forename: Ben
authors.initials: B
authors.lastname: Lane
mesh_terms: D001667:Binding, Competitive / Q000235:genetics; D005938:Glucocorticoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013489:Suppression, Genetic; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid