| Literature DB >> 29571573 |
Gilles Ouvry1, Franck Bihl2, Claire Bouix-Peter2, Olivier Christin2, Claire Defoin-Platel2, Sophie Deret2, Christophe Feret2, David Froude2, Feriel Hacini-Rachinel2, Craig S Harris2, Catherine Hervouet2, Guillaume Lafitte2, Anne-Pascale Luzy2, Branislav Musicki2, Danielle Orfila2, Veronique Parnet2, Coralie Pascau2, Jonathan Pascau2, Romain Pierre2, Catherine Raffin2, Patricia Rossio2, Delphine Spiesse2, Nathalie Taquet2, Etienne Thoreau2, Rodolphe Vatinel2, Emmanuel Vial2, Laurent F Hennequin2.
Abstract
Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model.Entities:
Keywords: Imiquimod; Psoriasis; RORγ; Sulfoximine; Topical application
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Year: 2018 PMID： 29571573 DOI： 10.1016/j.bmcl.2018.03.041
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823