Nestlé Skin Health R&D, 2400 Route des Colles, BP 87, 06902, Sophia-Antipolis Cedex, France.
ChemMedChem. 2018 Feb 20;13(4):321-337. doi: 10.1002/cmdc.201700758. Epub 2018 Feb 6.
With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ 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 in vivo activity in an IL-23-induced mouse skin inflammation model.
视黄酸受体相关孤儿受体 RORγ 可能与多种自身免疫性疾病有关，因此成为制药行业的热门靶点。本文介绍了鉴定一种与局部应用相容的、具有治疗皮肤病潜力的强效 RORγ 反向激动剂的努力。这些努力的最终成果是发现 N-(2,4-二甲基苯基)-N-异丁基-2-氧代-1-[(四氢-2H-吡喃-4-基)甲基]-2,3-二氢-1H-苯并[d]咪唑-5-磺酰胺（CD12681），这是一种强效的反向激动剂，在 IL-23 诱导的小鼠皮肤炎症模型中具有体内活性。
