- Small molecule amides as potent ROR-γ selective modulators.
Small molecule amides as potent ROR-γ selective modulators.
Bioorganic & medicinal chemistry letters (2012-12-13)
Pasha M Khan, Bahaa El-Dien M El-Gendy, Naresh Kumar, Ruben Garcia-Ordonez, Li Lin, Claudia H Ruiz, Michael D Cameron, Patrick R Griffin, Theodore M Kamenecka
PMID23232056
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.