Discovery and Characterization of CD12681, a Potent ROR Inverse Agonist, Preclinical Candidate for the Topical Treatment of Psoriasis

被引：13

作者：

Ouvry, Gilles ^{[1
]}

Atrux-Tallau, Nicolas ^{[1
]}

Bihl, Franck ^{[1
]}

Bondu, Aline ^{[1
]}

Bouix-Peter, Claire ^{[1
]}

Carlavan, Isabelle ^{[1
]}

Christin, Olivier ^{[1
]}

Cuadrado, Marie-Josee ^{[1
]}

Defoin-Platel, Claire ^{[1
]}

Deret, Sophie ^{[1
]}

Duvert, Denis ^{[1
]}

Feret, Christophe ^{[1
]}

Forissier, Mathieu ^{[1
]}

Fournier, Jean-Francois ^{[1
]}

Froude, David ^{[1
]}

Hacini-Rachinel, Feriel ^{[1
]}

Harris, Craig Steven ^{[1
]}

Hervouet, Catherine ^{[1
]}

Huguet, Helene ^{[1
]}

Lafitte, Guillaume ^{[1
]}

Luzy, Anne-Pascale ^{[1
]}

Musicki, Branislav ^{[1
]}

Orfila, Danielle ^{[1
]}

Ozello, Benjamin ^{[1
]}

Pascau, Coralie ^{[1
]}

Pascau, Jonathan ^{[1
]}

Parnet, Veronique ^{[1
]}

Peluchon, Guillaume ^{[1
]}

Pierre, Romain ^{[1
]}

Piwnica, David ^{[1
]}

Raffin, Catherine ^{[1
]}

Rossio, Patricia ^{[1
]}

Spiesse, Delphine ^{[1
]}

Taquet, Nathalie ^{[1
]}

Thoreau, Etienne ^{[1
]}

Vatinel, Rodolphe ^{[1
]}

Vial, Emmanuel ^{[1
]}

Hennequin, Laurent Francois ^{[1
]}

机构：

[1] Nestle Skin Hlth R&D, 2400 Route Colles,BP 87, F-06902 Sophia Antipolis, France

来源：

CHEMMEDCHEM | 2018年 / 13卷 / 04期

关键词：

interleukin17; lipophilic ligand efficiency; psoriasis; ROR; topical application; IN-VIVO; CELLS; MODULATORS; INHIBITORS; RECEPTOR; INFLAMMATION; DERMATITIS; EFFICACY; MODERATE; DESIGN;

D O I：

10.1002/cmdc.201700758

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor ROR has become a sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent ROR inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-[(tetrahydro-2H-pyran-4-yl)methyl]-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (CD12681), a potent inverse agonist with invivo activity in an IL-23-induced mouse skin inflammation model.

引用

页码：321 / 337

页数：17

共 9 条

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