4-(3-(2,6-dichlorophenoxy)-1H-indazol-1-yl)-3-fluorobenzoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3-(2,6-dichlorophenoxy)-1H-indazol-1-yl)-3-fluorobenzoic acid
• 英文别名: 4-[3-(2,6-dichlorophenoxy)-1H-indazol-1-yl]-3-fluorobenzoic acid；4-[3-(2,6-Dichlorophenoxy)indazol-1-yl]-3-fluorobenzoic acid；4-[3-(2,6-dichlorophenoxy)indazol-1-yl]-3-fluorobenzoic acid
• 化学式: C₂₀H₁₁Cl₂FN₂O₃
• 分子量: 417.223
• InChiKey: SVWMRFBEGOFZSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3-二氯硝基苯 在 铁粉 、 caesium carbonate 、 溶剂黄146 、 copper dichloride 、 亚硝酸异戊酯 作用下， 以 乙腈 为溶剂， 反应 25.5h， 生成 4-(3-(2,6-dichlorophenoxy)-1H-indazol-1-yl)-3-fluorobenzoic acid
  参考文献：
  名称：

  Discovery of phenoxyindazoles and phenylthioindazoles as RORγ inverse agonists

  摘要：

  Targeting the IL17 pathway and more specifically the nuclear receptor ROR gamma is thought to be beneficial in multiple skin disorders. The Letter describes the discovery of phenoxyindazoles and thiophenoxy indazoles as potent ROR gamma inverse agonists. Optimization of the potency and efforts to mitigate the phototoxic liability of the series are presented. Finally, crystallization of the lead compound revealed that the series bound to an allosteric site of the nuclear receptor. Such compounds could be useful as tool compounds for understanding the impact of topical treatment on skin disease models. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.023

文献信息

• [EN] BICYCLIC HETEROARYL INDOLE ANALOGUES USEFUL AS ROR GAMMA MODULATORS<br/>[FR] ANALOGUES DE L'INDOLE HÉTEROARYLE BICYCLIQUE UTILES EN TANT QUE MODULATEURS DE GAMMA ROR
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2015087234A1

  公开（公告）日：2015-06-18

  The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X, X1, M, R2, R3, R4, R5, m, n, and p are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, neurodegenerative diseases and cancer.

  本公开涉及式(I)的化合物及其药用盐，其中X、X1、M、R2、R3、R4、R5、m、n和p如本文所定义，这些化合物作为视黄醇相关孤儿受体γt（RORγt）调节剂具有活性。这些化合物可以预防、抑制或抑制RORγt的作用，因此在治疗RORγt介导的疾病、疾病、综合症或病况中具有用处，例如疼痛、炎症、慢性阻塞性肺病（COPD）、哮喘、类风湿关节炎、结肠炎、多发性硬化症、神经退行性疾病和癌症。
• BICYCLIC HETEROARYL INDOLE ANALOGUES USEFUL AS ROR GAMMA MODULATORS
  申请人：Glenmark Pharmaceuticals S.A.

  公开号：EP3080090A1

  公开（公告）日：2016-10-19
• US9682977B2
  申请人：——

  公开号：US9682977B2

  公开（公告）日：2017-06-20
• Discovery of phenoxyindazoles and phenylthioindazoles as RORγ inverse agonists
  作者：Gilles Ouvry、Claire Bouix-Peter、Fabrice Ciesielski、Laurent Chantalat、Olivier Christin、Catherine Comino、Denis Duvert、Christophe Feret、Craig S. Harris、Laurent Lamy、Anne-Pascale Luzy、Branislav Musicki、Danielle Orfila、Jonathan Pascau、Véronique Parnet、Agnès Perrin、Romain Pierre、Gaëlle Polge、Catherine Raffin、Yves Rival、Nathalie Taquet、Etienne Thoreau、Laurent F. Hennequin

  DOI：10.1016/j.bmcl.2016.10.023

  日期：2016.12

  Targeting the IL17 pathway and more specifically the nuclear receptor ROR gamma is thought to be beneficial in multiple skin disorders. The Letter describes the discovery of phenoxyindazoles and thiophenoxy indazoles as potent ROR gamma inverse agonists. Optimization of the potency and efforts to mitigate the phototoxic liability of the series are presented. Finally, crystallization of the lead compound revealed that the series bound to an allosteric site of the nuclear receptor. Such compounds could be useful as tool compounds for understanding the impact of topical treatment on skin disease models. (C) 2016 Elsevier Ltd. All rights reserved.