title: Synthesis and structure-activity relationships of novel indazolyl glucocorticoid receptor partial agonists.
abstract: SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors.
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA. john.gilmore@bms.com
authors.forename: John L
authors.initials: JL
authors.lastname: Gilmore
authors.forename: James E
authors.initials: JE
authors.lastname: Sheppeck
authors.forename: Jim
authors.initials: J
authors.lastname: Wang
authors.forename: T G Murali
authors.initials: TG
authors.lastname: Dhar
authors.forename: Cullen
authors.initials: C
authors.lastname: Cavallaro
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Doweyko
authors.forename: Lorraine
authors.initials: L
authors.lastname: Mckay
authors.forename: Mark D
authors.initials: MD
authors.lastname: Cunningham
authors.forename: Sium F
authors.initials: SF
authors.lastname: Habte
authors.forename: Steven G
authors.initials: SG
authors.lastname: Nadler
authors.forename: John H
authors.initials: JH
authors.lastname: Dodd
authors.forename: John E
authors.initials: JE
authors.lastname: Somerville
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D011485:Protein Binding / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D014508:Urea / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D007191:Indazoles; D011965:Receptors, Glucocorticoid; D013449:Sulfonamides; D014508:Urea
keywords: Dissociated; GR agonist; Glucocortocoids; Selective GR agonist