ethyl 3-{5-[(N'-hydroxyamino)(imino)methyl]-1H-indazol-1-yl}propanoate | 1072947-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: ethyl 3-{5-[(N'-hydroxyamino)(imino)methyl]-1H-indazol-1-yl}propanoate
• 英文别名: ethyl 3-{5-[(hydroxyamino)(imino)methyl]-1H-indazol-1-yl}propanoate；Ethyl 3-{5-[(hydroxyamino)(imino)methyl]-1H-indazol-1-yl}propanoate；ethyl 3-[5-(N'-hydroxycarbamimidoyl)indazol-1-yl]propanoate
• CAS: 1072947-79-5
• 化学式: C₁₃H₁₆N₄O₃
• 分子量: 276.295
• InChiKey: ALUBEUGKSWBKAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-异丙氧基-3-(三氟甲基)苯甲酸 、 ethyl 3-{5-[(N'-hydroxyamino)(imino)methyl]-1H-indazol-1-yl}propanoate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 3-(5-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indazol-1-yl)propanoate
  参考文献：
  名称：

  WO2008/128951

  摘要：

  公开号：
• 作为产物：
  描述：

  5-氰基-2-氟苯甲醛 在 盐酸羟胺 、 碳酸氢钠 、 potassium carbonate 、 caesium carbonate 、 肼 作用下， 以 乙醇 、 2-甲基戊烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 ethyl 3-{5-[(N'-hydroxyamino)(imino)methyl]-1H-indazol-1-yl}propanoate
  参考文献：
  名称：

  OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS

  摘要：

  氧代唑取代吲唑衍生物的化学式（I）或其药用盐具有药理活性，公开了它们的制备方法、含有它们的药物组合物以及它们在治疗由S1P1受体介导的各种疾病中的用途。

  公开号：

  US20120283297A1

文献信息

• [EN] OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS<br/>[FR] DÉRIVÉS D'INDAZOLE SUBSTITUÉS PAR OXADIAZOLE DESTINÉS À ÊTRE UTILISÉS COMME AGONISTES DU RÉCEPTEUR DE SPHINGOSINE-1-PHOSPHATE 1 (S1P1)
  申请人：GLAXO GROUP LTD

  公开号：WO2011072488A1

  公开（公告）日：2011-06-23

  Oxadiazole substituted indazole derivatives of formula (I) or pharmaceutical salts thereof having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their uses in the treatment of various disorders mediated by S1P1 receptor are disclosed.

  氧代唑取代吲唑衍生物的化学式（I）或其药用盐具有药理活性，公开了它们的制备方法、含有它们的药物组合物以及它们在治疗由S1P1受体介导的各种疾病中的用途。
• OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE (S1P) AGONISTS
  申请人：Ahmed Mahmood

  公开号：US20100113528A1

  公开（公告）日：2010-05-06

  The present invention provides compounds of formula (I) or salts thereof: having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders mediated by S1P1 receptors.

  本发明提供式（I）的化合物或其盐：具有药理活性，它们的制备过程，包含它们的制药组合物以及它们在治疗由S1P1受体介导的各种疾病中的应用。
• Oxadiazole substituted indazole derivatives for use as sphingosine 1-phosphate (S1P) agonists
  申请人：Glaxo Group Limited

  公开号：US08324254B2

  公开（公告）日：2012-12-04

  The present invention provides compounds of formula (I) or salts thereof: having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders mediated by S1P1 receptors.

  本发明提供公式（I）的化合物或其盐：具有药理活性，其制备过程，含有它们的制药组合物以及它们在治疗由S1P1受体介导的各种疾病中的使用。
• Optimization of Sphingosine-1-phosphate-1 Receptor Agonists: Effects of Acidic, Basic, and Zwitterionic Chemotypes on Pharmacokinetic and Pharmacodynamic Profiles
  作者：John Skidmore、Jag Heer、Christopher N. Johnson、David Norton、Sally Redshaw、Jennifer Sweeting、David Hurst、Andrew Cridland、David Vesey、Ian Wall、Mahmood Ahmed、Dean Rivers、James Myatt、Gerard Giblin、Karen Philpott、Umesh Kumar、Alexander Stevens、Rino A. Bit、Andrea Haynes、Simon Taylor、Robert Watson、Jason Witherington、Emmanuel Demont、Tom D. Heightman

  DOI：10.1021/jm5010336

  日期：2014.12.26

  The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P(1) receptors, while a variety of side effects have been ascribed to its S1P(3) receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P(1) receptor agonism. Here we describe a study of the tolerance of the S1P(1) and S1P(3) receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P(1) receptor agonists with good selectivity vs S1P(3) receptors, efficacy at <1 mg/kg oral doses, and developability properties suitable for progression into preclinical development.
• EP2137181B1
  申请人：——

  公开号：EP2137181B1

  公开（公告）日：2011-03-02