3-Hydroxy-3-methyl-butansaeureamid | 88512-09-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3-Hydroxy-3-methyl-butansaeureamid
• 英文别名: 3-Hydroxy-3-methyl-buttersaeureamid；3-Hydroxy-isovaleriansaeureamid；β-hydroxy-isovaleric acid amide；3-Hydroxy-3-methyl-butyramid；β-Hydroxy-isovaleriansaeure-amid；3-hydroxyisovaleramide；3-Hydroxy-3-methylbutanamide
• CAS: 88512-09-8
• 化学式: C₅H₁₁NO₂
• mdl: MFCD19203969
• 分子量: 117.148
• InChiKey: QHNHAWNULKRVMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-Hydroxy-3-methyl-butansaeureamid 、 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50%的产率得到N-[[4-(4-fluorophenyl)sulfonyl-7-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2,3-dihydro-1,4-benzothiazin-2-yl]methyl]-3-hydroxy-3-methylbutanamide
  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
• 作为产物：
  描述：

  4,4-二甲基-2-氧杂环丁酮 在 氨 、 水 作用下， 生成 3-Hydroxy-3-methyl-butansaeureamid
  参考文献：
  名称：

  β-Propiolactone. XIV.¹ β-Isovalerolactone

  摘要：

  DOI：

  10.1021/ja01631a045

文献信息

• Graf,R., Justus Liebigs Annalen der Chemie, 1963, vol. 661, p. 111 - 157
  作者：Graf,R.

  DOI：——

  日期：——
• β-Propiolactone. XIV.¹ β-Isovalerolactone
  作者：T. L. Gresham、J. E. Jansen、F. W. Shaver、W. L. Beears

  DOI：10.1021/ja01631a045

  日期：1954.1
• 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.