title: Small molecule amides as potent ROR-γ selective modulators.
abstract: The structure-activity relationship study of a diphenylpropanamide series of ROR-γ selective modulators is reported. Compounds were screened using chimeric receptor Gal4 DNA-binding domain (DBD)-NR ligand binding domain cotransfection assay in a two-step format. Three different regions of the scaffold were modified to assess the effects on repression of ROR-γ transcriptional activity and potency. The lead compound 1 exhibits modest mouse pharmacokinetics and an acceptable in vitro profile which makes it a suitable in vivo probe to interrogate the functions of ROR-γ in animal models of disease.
authors.affiliation: Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors.forename: Pasha M
authors.initials: PM
authors.lastname: Khan
authors.forename: Bahaa El-Dien M
authors.initials: Bel-D
authors.lastname: El-Gendy
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
authors.forename: Ruben
authors.initials: R
authors.lastname: Garcia-Ordonez
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Claudia H
authors.initials: CH
authors.lastname: Ruiz
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cameron
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Griffin
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Kamenecka
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D054852:Small Molecule Libraries; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001713:Biphenyl Compounds; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D054852:Small Molecule Libraries; C010574:biphenyl