TO901317 | 293753-88-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: TO901317
• 英文别名: T0901317；N-ethyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide
• CAS: 293753-88-5
• 化学式: C₁₇H₁₅F₆NO₃S
• 分子量: 427.367
• InChiKey: IVNRPSKTRKQRGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-(4-氨基苯)-1,1,1,3,3,3-六氟-2-丙醇 在 2,6-二甲基吡啶 、 potassium carbonate 作用下， 以 丙酮 、 乙腈 为溶剂， 生成 TO901317
  参考文献：
  名称：

  Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc

  摘要：

  The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors.

  DOI：

  10.1016/j.bmcl.2013.10.054

文献信息

• MODULATORS OF RETINOID-RELATED ORPHAN RECEPTOR GAMMA
  申请人：Orphagen Pharmaceuticals

  公开号：US20130150333A1

  公开（公告）日：2013-06-13

  Methods for modulating (inhibiting or stimulating) retinoid-related orphan receptor γ (RORγ) activity. This modulation has numerous effects, including inhibition of T H -17 cell function and/or T H -17 cell activity, and inhibition of re-stimulation of T H -17 cells, which are beneficial to treatment of inflammation and autoimmune disorders. Stimulation of RORγ results in stimulation of T H -17 cell function and/or activity which is beneficial for immune-enhancing compositions (e.g., vaccines).

  调节（抑制或刺激）视黄醇相关孤儿受体γ（RORγ）活性的方法。这种调节具有许多效果，包括抑制TH-17细胞功能和/或TH-17细胞活性，以及抑制TH-17细胞再激活，这对治疗炎症和自身免疫性疾病有益。刺激RORγ会导致TH-17细胞功能和/或活性的刺激，这对于免疫增强组合物（例如疫苗）有益。
• [EN] 2-OXO-1,2-DIHYDROBENZO[CD]INDOLE-6-SULFONAMIDE COMPOUND AND COMPOSITION AND USE THEREOF<br/>[FR] COMPOSÉ 2-OXO-1,2-DIHYDROBENZO[CD]INDOLE-6-SULFONAMIDE ET COMPOSITION ET UTILISATION CORRESPONDANTES<br/>[ZH] 2-氧代-1,2-二氢苯并[cd]吲哚-6-磺酰胺类化合物及其组合物和应用
  申请人：GUANGZHOU INST BIOMED & HEALTH

  公开号：WO2015096771A1

  公开（公告）日：2015-07-02

  本发明提供了具有通式I结构特征的化合物作为新型的维甲酸孤儿核受体γ亚型（RORγ）抑制剂，以及该类化合物及其药学上可接受的盐、异构体、外消旋体、前体药物共结晶复合物、水合物、溶剂合物在治疗或预防RORγ调控的相关疾病的药物中的应用。
• US8389739B1
  申请人：——

  公开号：US8389739B1

  公开（公告）日：2013-03-05
• US9657053B2
  申请人：——

  公开号：US9657053B2

  公开（公告）日：2017-05-23
• Structure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc
  作者：Benjamin P. Fauber、Gladys de Leon Boenig、Brenda Burton、Céline Eidenschenk、Christine Everett、Alberto Gobbi、Sarah G. Hymowitz、Adam R. Johnson、Marya Liimatta、Peter Lockey、Maxine Norman、Wenjun Ouyang、Olivier René、Harvey Wong

  DOI：10.1016/j.bmcl.2013.10.054

  日期：2013.12

  The structure-activity relationships of T0901317 analogs were explored as RORc inverse agonists using the principles of property- and structure-based drug design. An X-ray co-crystal structure of T0901317 and RORc was obtained and provided molecular insight into why T0901317 functioned as an inverse agonist of RORc; whereas, the same ligand functioned as an agonist of FXR, LXR, and PXR. The structural data was also used to design inhibitors with improved RORc biochemical and cellular activities. The improved inhibitors possessed enhanced selectivity profiles (rationalized using the X-ray crystallographic data) against other nuclear receptors.