4-(3-((2,5-dichlorophenyl)thio)-5-(dimethylcarbamoyl)-1H-indazol-1-yl)benzoic 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-((2,5-dichlorophenyl)thio)-5-(dimethylcarbamoyl)-1H-indazol-1-yl)benzoic acid
• 英文别名: 4-[3-(2,5-Dichlorophenyl)sulfanyl-5-(dimethylcarbamoyl)indazol-1-yl]benzoic acid；4-[3-(2,5-dichlorophenyl)sulfanyl-5-(dimethylcarbamoyl)indazol-1-yl]benzoic acid
• 化学式: C₂₃H₁₇Cl₂N₃O₃S
• 分子量: 486.378
• InChiKey: BBYSACCQLXWXSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-碘-5-吲唑羧酸甲酯 在 N-甲基吡咯烷酮 、 copper(l) iodide 、 caesium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 三氟乙酸 、 聚二(乙氧基吡咯烷酮)膦腈 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 36.5h， 生成 4-(3-((2,5-dichlorophenyl)thio)-5-(dimethylcarbamoyl)-1H-indazol-1-yl)benzoic 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

• 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.