Small molecule amides as potent ROR-γ selective modulators

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

doi:10.1016/j.bmcl.2012.11.025

Small molecule amides as potent ROR-γ selective modulators

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

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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.

Original language	English
Pages (from-to)	532-536
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2012.11.025
State	Published - Jan 15 2013

Keywords

Diphenylpropanamide
Nuclear hormone receptor
ROR-γ selective
SAR

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10.1016/j.bmcl.2012.11.025

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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.",

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AU - El-Gendy, Bahaa El Dien M.

AU - Kumar, Naresh

AU - Garcia-Ordonez, Ruben

AU - Lin, Li

AU - Ruiz, Claudia H.

AU - Cameron, Michael D.

AU - Griffin, Patrick R.

AU - Kamenecka, Theodore M.

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KW - Diphenylpropanamide

KW - Nuclear hormone receptor

KW - ROR-γ selective

KW - SAR

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Small molecule amides as potent ROR-γ selective modulators

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Keywords

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