tert-butyl (S)-2-(4-(4-phenylphenethyloxy)-3-(trifluoromethyl)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamate | 876914-76-0

• 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: tert-butyl (S)-2-(4-(4-phenylphenethyloxy)-3-(trifluoromethyl)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamate
• 英文别名: tert-butyl N-[(2S)-3-hydroxy-2-methyl-1-oxo-1-[4-[2-(4-phenylphenyl)ethoxy]-3-(trifluoromethyl)anilino]propan-2-yl]carbamate
• CAS: 876914-76-0
• 化学式: C₃₀H₃₃F₃N₂O₅
• 分子量: 558.598
• InChiKey: IDIIHCPQMNFRQA-LJAQVGFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  96.9
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-2-(4-(4-phenylphenethyloxy)-3-(trifluoromethyl)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-N-(4-(4-phenylphenethyloxy)-3-(trifluoromethyl)phenyl)-2-amino-3-hydroxy-2-methylpropanamide
  参考文献：
  名称：

  Exploration of amino alcohol derivatives as novel, potent, and highly selective sphingosine-1-phosphate receptor subtype-1 agonists

  摘要：

  In pursuit of a potent and highly selective sphingosine-1-phosphate receptor agonists with an improved in vivo conversion of the precursor to the active phospho-drug, we have utilized previously reported phenylamide and phenylimidazole scaffolds to identify a selectivity enhancing moiety (SEM) and selectivity enhancing orientation (SEO) within both pharmacophores. SEM and SEO have allowed for over 100 to 500-fold improvement in selectivity for S1P receptor subtype 1 over subtype 3. Utility of SEM and SEO and further SAR study allowed for discovery of a potent and selective preclinical candidate PPI-4955 (21b) with an excellent in vivo potency and dose responsiveness and markedly improved overall in vivo pharmacodynamic properties upon oral administration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.098
• 作为产物：
  描述：

  4-(2-([1,1'-biphenyl]-4-yl)ethoxy)-3-(trifluoromethyl)aniline 、 N-BOC-2-甲基-L-丝氨酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (S)-2-(4-(4-phenylphenethyloxy)-3-(trifluoromethyl)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamate
  参考文献：
  名称：

  Exploration of amino alcohol derivatives as novel, potent, and highly selective sphingosine-1-phosphate receptor subtype-1 agonists

  摘要：

  In pursuit of a potent and highly selective sphingosine-1-phosphate receptor agonists with an improved in vivo conversion of the precursor to the active phospho-drug, we have utilized previously reported phenylamide and phenylimidazole scaffolds to identify a selectivity enhancing moiety (SEM) and selectivity enhancing orientation (SEO) within both pharmacophores. SEM and SEO have allowed for over 100 to 500-fold improvement in selectivity for S1P receptor subtype 1 over subtype 3. Utility of SEM and SEO and further SAR study allowed for discovery of a potent and selective preclinical candidate PPI-4955 (21b) with an excellent in vivo potency and dose responsiveness and markedly improved overall in vivo pharmacodynamic properties upon oral administration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.098

文献信息

• Methods and compositions for modulating sphingosine -1- phosphate (S1P) receptor activity
  申请人：Saha K. Ashis

  公开号：US20080064662A1

  公开（公告）日：2008-03-13

  The present invention relates to compounds which modulate the activity of the S1P1 receptor, the use of these compounds for treating conditions associated with signaling through the S1P1 receptor, and pharmaceutical compositions comprising these compounds.

  本发明涉及调节S1P1受体活性的化合物，使用这些化合物治疗与S1P1受体信号有关的疾病，并包括这些化合物的制药组合物。
• US7241812B2
  申请人：——

  公开号：US7241812B2

  公开（公告）日：2007-07-10
• Exploration of amino alcohol derivatives as novel, potent, and highly selective sphingosine-1-phosphate receptor subtype-1 agonists
  作者：Ghotas Evindar、Sylvie G. Bernier、Elisabeth Doyle、Malcolm J. Kavarana、Alexander L. Satz、Jeanine Lorusso、Heather S. Blanchette、Ashis K. Saha、Gerhard Hannig、Barry A. Morgan、William F. Westlin

  DOI：10.1016/j.bmcl.2010.02.098

  日期：2010.4

  In pursuit of a potent and highly selective sphingosine-1-phosphate receptor agonists with an improved in vivo conversion of the precursor to the active phospho-drug, we have utilized previously reported phenylamide and phenylimidazole scaffolds to identify a selectivity enhancing moiety (SEM) and selectivity enhancing orientation (SEO) within both pharmacophores. SEM and SEO have allowed for over 100 to 500-fold improvement in selectivity for S1P receptor subtype 1 over subtype 3. Utility of SEM and SEO and further SAR study allowed for discovery of a potent and selective preclinical candidate PPI-4955 (21b) with an excellent in vivo potency and dose responsiveness and markedly improved overall in vivo pharmacodynamic properties upon oral administration. (C) 2010 Elsevier Ltd. All rights reserved.