title: Dimethyl-diphenyl-propanamide derivatives as nonsteroidal dissociated glucocorticoid receptor agonists.
abstract: A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed.
authors.affiliation: Bristol-Myers Squibb Company, Research and Development, Princeton, New Jersey 08543-4000, United States.
authors.forename: Bingwei V
authors.initials: BV
authors.lastname: Yang
authors.forename: David S
authors.initials: DS
authors.lastname: Weinstein
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Doweyko
authors.forename: Hua
authors.initials: H
authors.lastname: Gong
authors.forename: Wayne
authors.initials: W
authors.lastname: Vaccaro
authors.forename: Tram
authors.initials: T
authors.lastname: Huynh
authors.forename: Hai-Yun
authors.initials: HY
authors.lastname: Xiao
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Doweyko
authors.forename: Lorraine
authors.initials: L
authors.lastname: McKay
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Holloway
authors.forename: John E
authors.initials: JE
authors.lastname: Somerville
authors.forename: Sium
authors.initials: S
authors.lastname: Habte
authors.forename: Mark
authors.initials: M
authors.lastname: Cunningham
authors.forename: Michele
authors.initials: M
authors.lastname: McMahon
authors.forename: Robert
authors.initials: R
authors.lastname: Townsend
authors.forename: David
authors.initials: D
authors.lastname: Shuster
authors.forename: John H
authors.initials: JH
authors.lastname: Dodd
authors.forename: Steven G
authors.initials: SG
authors.lastname: Nadler
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D008958:Models, Molecular; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000819:agonists*
chemical_list: D000577:Amides; D011965:Receptors, Glucocorticoid