1-(2-piperidin-1-yl-ethyl)-1H-indazol-5-ylamine | 854921-76-9

• 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: 1-(2-piperidin-1-yl-ethyl)-1H-indazol-5-ylamine
• 英文别名: 1-(2-piperidin-1-ylethyl)indazol-5-amine
• CAS: 854921-76-9
• 化学式: C₁₄H₂₀N₄
• 分子量: 244.34
• InChiKey: PJQQVQGTOGGPRT-UHFFFAOYSA-N

物化性质

• 沸点：
  433.6±25.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-piperidin-1-yl-ethyl)-1H-indazol-5-ylamine 、 4-苯氧基苯基异氰酸酯 以 四氢呋喃 为溶剂， 反应 1.0h， 以80%的产率得到1-(4-phenoxy-phenyl)-3-[1-(2-piperidin-1-yl-ethyl)-1H-indazol-5-yl]-urea
  参考文献：
  名称：

  Screening for Cardiovascular Safety:  A Structure−Activity Approach for Guiding Lead Selection of Melanin Concentrating Hormone Receptor 1 Antagonists

  摘要：

  An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening mode to triage multiple classes of melanin-concentrating hormone receptor I (MCHr1) antagonists. Lead identification was based on a compound profile producing high drug concentration in both plasma (> 40 mu M) and brain (> 20 mu g/g) with < 15% change in cardiovascular endpoints. As a result of these stringent requirements, lead optimization activities on multiple classes of MCHr1 antagonists were terminated. After providing evidence that the cardiovascular liabilities were not a function of MCHr1 antagonism, continued screening identified the chromone-substituted aminopiperidine amides as a class of MCHr1 antagonists that demonstrated a safe cardiovascular profile at high drug concentrations in both plasma and brain. The high incidence of adverse cardiovascular effects associated with an array of MCHrl antagonists of significant chemical diversity, combined with the stringent safety requirements for antiobesity drugs, highlight the importance of incorporating cardiovascular safety assessment early in the lead selection process.

  DOI：

  10.1021/jm0512286
• 作为产物：
  描述：

  4-硝基-2-甲苯胺 在 铁粉 、 potassium carbonate 、 氯化铵 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-(2-piperidin-1-yl-ethyl)-1H-indazol-5-ylamine
  参考文献：
  名称：

  Screening for Cardiovascular Safety:  A Structure−Activity Approach for Guiding Lead Selection of Melanin Concentrating Hormone Receptor 1 Antagonists

  摘要：

  An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening mode to triage multiple classes of melanin-concentrating hormone receptor I (MCHr1) antagonists. Lead identification was based on a compound profile producing high drug concentration in both plasma (> 40 mu M) and brain (> 20 mu g/g) with < 15% change in cardiovascular endpoints. As a result of these stringent requirements, lead optimization activities on multiple classes of MCHr1 antagonists were terminated. After providing evidence that the cardiovascular liabilities were not a function of MCHr1 antagonism, continued screening identified the chromone-substituted aminopiperidine amides as a class of MCHr1 antagonists that demonstrated a safe cardiovascular profile at high drug concentrations in both plasma and brain. The high incidence of adverse cardiovascular effects associated with an array of MCHrl antagonists of significant chemical diversity, combined with the stringent safety requirements for antiobesity drugs, highlight the importance of incorporating cardiovascular safety assessment early in the lead selection process.

  DOI：

  10.1021/jm0512286

文献信息

• Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor
  申请人：Souers J. Andrew

  公开号：US20050137243A1

  公开（公告）日：2005-06-23

  The present invention relates to the antagonism of the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor which is useful for the prevention or treatment of eating disorders, weight gain, obesity, abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders.

  本发明涉及通过黑色素浓缩激素受体对黑色素浓缩激素（MCH）效应的拮抗，该拮抗对预防或治疗进食障碍、体重增加、肥胖、生殖和性行为异常、甲状腺激素分泌、利尿和水/电解质平衡、感觉处理、记忆、睡眠、唤醒、焦虑、抑郁、癫痫、神经退行性疾病和精神疾病有用。
• Design, synthesis and anticancer activity evaluation of novel C14 heterocycle substituted epi-triptolide
  作者：Hongtao Xu、Huanyu Tang、Huijin Feng、Yuanchao Li

  DOI：10.1016/j.ejmech.2013.11.044

  日期：2014.2

  Two series of novel C14 heterocycle substituted epi-triptolide derivatives as potential anticancer agents were synthesized and tested for their cytotoxicity against SKOV-3 and PC-3 tumor cell lines. The introduction of C14 beta-aryl heterocycle aminomethyl substituent to the leading compound was found to be an effective modification method to retain the potent anticancer activity. Meanwhile, the series of epitriptolide derivatives (21-40) with C14 alpha-hydroxyl group, still retained the natural product's cytotoxicity. This is apparently challenges the classical structure activity relationship of triptolide that considers the C14 beta-hydroxyl group to be essential for its anticancer activity. (C) 2013 Elsevier Masson SAS. All rights reserved.
• US7071182B2
  申请人：——

  公开号：US7071182B2

  公开（公告）日：2006-07-04
• Screening for Cardiovascular Safety:  A Structure−Activity Approach for Guiding Lead Selection of Melanin Concentrating Hormone Receptor 1 Antagonists
  作者：Philip R. Kym、Andrew J. Souers、Thomas J. Campbell、John K. Lynch、Andrew S. Judd、Rajesh Iyengar、Anil Vasudevan、Ju Gao、Jennifer C. Freeman、Dariusz Wodka、Mathew Mulhern、Gang Zhao、Seble H. Wagaw、James J. Napier、Sevan Brodjian、Brian D. Dayton、Regina M. Reilly、Jason A. Segreti、Ryan M. Fryer、Lee C. Preusser、Glenn A. Reinhart、Lisa Hernandez、Kennan C. Marsh、Hing L. Sham、Christine A. Collins、James S. Polakowski

  DOI：10.1021/jm0512286

  日期：2006.4.1

  An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening mode to triage multiple classes of melanin-concentrating hormone receptor I (MCHr1) antagonists. Lead identification was based on a compound profile producing high drug concentration in both plasma (> 40 mu M) and brain (> 20 mu g/g) with < 15% change in cardiovascular endpoints. As a result of these stringent requirements, lead optimization activities on multiple classes of MCHr1 antagonists were terminated. After providing evidence that the cardiovascular liabilities were not a function of MCHr1 antagonism, continued screening identified the chromone-substituted aminopiperidine amides as a class of MCHr1 antagonists that demonstrated a safe cardiovascular profile at high drug concentrations in both plasma and brain. The high incidence of adverse cardiovascular effects associated with an array of MCHrl antagonists of significant chemical diversity, combined with the stringent safety requirements for antiobesity drugs, highlight the importance of incorporating cardiovascular safety assessment early in the lead selection process.