(S)-4-amino-3-fluoro-2-methylbutan-2-ol | 1609546-50-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (S)-4-amino-3-fluoro-2-methylbutan-2-ol
• 英文别名: (3S)-4-Amino-3-fluoro-2-methylbutan-2-ol；(3S)-4-amino-3-fluoro-2-methylbutan-2-ol
• CAS: 1609546-50-0
• 化学式: C₅H₁₂FNO
• 分子量: 121.155
• InChiKey: QNFKDKWENVIYDB-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-4-amino-3-fluoro-2-methylbutan-2-ol 、 (S)-2-(1-((4-fluorophenyl)sulfonyl)-6-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,2,3,4-tetrahydroquinolin-2-yl)acetic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以58%的产率得到N-((S)-2-fluoro-3-hydroxy-3-methylbutyl)-2-((S)-1-((4-fluorophenyl)sulfonyl)-6-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,2,3,4-tetrahydroquinolin-2-yl)acetamide
  参考文献：
  名称：

  Identification of bicyclic hexafluoroisopropyl alcohol sulfonamides as retinoic acid receptor-related orphan receptor gamma (RORγ/RORc) inverse agonists. Employing structure-based drug design to improve pregnane X receptor (PXR) selectivity

  摘要：

  We disclose the optimization of a high throughput screening hit to yield benzothiazine and tetrahydroquinoline sulfonamides as potent ROR gamma t inverse agonists. However, a majority of these compounds showed potent activity against pregnane X receptor (PXR) and modest activity against liver X receptor alpha (LXR alpha). Structure-based drug design (SBDD) led to the identification of benzothiazine and tetrahydro-quinoline sulfonamide analogs which completely dialed out LXR alpha activity and were less potent at PXR. Pharmacodynamic (PD) data for compound 35 in an IL-23 induced IL-17 mouse model is discussed along with the implications of a high Y-max in the PXR assay for long term preclinical pharmacokinetic (PK) studies. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.12.006

文献信息

• Identification of bicyclic hexafluoroisopropyl alcohol sulfonamides as retinoic acid receptor-related orphan receptor gamma (RORγ/RORc) inverse agonists. Employing structure-based drug design to improve pregnane X receptor (PXR) selectivity
  作者：Hua Gong、David S. Weinstein、Zhonghui Lu、James J.-W. Duan、Sylwia Stachura、Lauren Haque、Ananta Karmakar、Hemalatha Hemagiri、Dhanya Kumar Raut、Arun Kumar Gupta、Javed Khan、Dan Camac、John S. Sack、Andrew Pudzianowski、Dauh-Rurng Wu、Melissa Yarde、Ding-Ren Shen、Virna Borowski、Jenny H. Xie、Huadong Sun、Celia D'Arienzo、Marta Dabros、Michael A. Galella、Faye Wang、Carolyn A. Weigelt、Qihong Zhao、William Foster、John E. Somerville、Luisa M. Salter-Cid、Joel C. Barrish、Percy H. Carter、T.G. Murali Dhar

  DOI：10.1016/j.bmcl.2017.12.006

  日期：2018.1

  We disclose the optimization of a high throughput screening hit to yield benzothiazine and tetrahydroquinoline sulfonamides as potent ROR gamma t inverse agonists. However, a majority of these compounds showed potent activity against pregnane X receptor (PXR) and modest activity against liver X receptor alpha (LXR alpha). Structure-based drug design (SBDD) led to the identification of benzothiazine and tetrahydro-quinoline sulfonamide analogs which completely dialed out LXR alpha activity and were less potent at PXR. Pharmacodynamic (PD) data for compound 35 in an IL-23 induced IL-17 mouse model is discussed along with the implications of a high Y-max in the PXR assay for long term preclinical pharmacokinetic (PK) studies. (C) 2017 Elsevier Ltd. All rights reserved.