1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-ylamine | 848779-68-0

• 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-pyrrolidin-1-ylethyl)-1H-indazol-4-ylamine
• 英文别名: 1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-4-ylamine；1-(2-pyrrolidin-1-ylethyl)indazol-4-amine
• CAS: 848779-68-0
• 化学式: C₁₃H₁₈N₄
• 分子量: 230.313
• InChiKey: ICTBJQFRVQXRQS-UHFFFAOYSA-N

物化性质

• 沸点：
  421.3±25.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 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-pyrrolidin-1-ylethyl)-1H-indazol-4-ylamine 、 4-苄氧基苯乙酸 在 N-甲基吗啉 、 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 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 6.0h， 生成 2-[4-(benzyloxy)phenyl]-N-[1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-yl]acetamide
  参考文献：
  名称：

  Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor

  摘要：

  本发明涉及通过黑素浓缩激素（MCH）受体对黑素浓缩激素效应的拮抗，用于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/电解质稳态、感觉处理、记忆、睡眠、觉醒、焦虑、抑郁、癫痫、神经退行性疾病和精神障碍。

  公开号：

  US20050277638A1
• 作为产物：
  描述：

  4-硝基吲唑 在 铁粉 、 potassium carbonate 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-ylamine
  参考文献：
  名称：

  尿素基吲唑类化合物作为黑色素浓缩激素受体1拮抗剂的合成与评价。

  摘要：

  合成了一系列基于尿素的N-1-（2-氨基乙基）-吲唑，并在结合和功能试验中评估了其对黑色素浓缩激素受体1（MCHr1）的拮抗作用。鉴定了几种充当MCHr1拮抗剂的化合物，在饮食引起的肥胖小鼠体重减轻的慢性模型中，优化后得到了一种具有出色的结合亲和力，良好的功能效价和口服功效的化合物。

  DOI：

  10.1016/j.bmcl.2005.03.114

文献信息

• 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.
• Identification of 2-(4-Benzyloxyphenyl)-<i>N</i>- [1-(2-pyrrolidin-1-yl-ethyl)-1<i>H</i>-indazol-6-yl]acetamide, an Orally Efficacious Melanin-Concentrating Hormone Receptor 1 Antagonist for the Treatment of Obesity
  作者：Andrew J. Souers、Ju Gao、Michael Brune、Eugene Bush、Dariusz Wodka、Anil Vasudevan、Andrew S. Judd、Mathew Mulhern、Sevan Brodjian、Brian Dayton、Robin Shapiro、Lisa E. Hernandez、Kennan C. Marsh、Hing L. Sham、Christine A. Collins、Philip R. Kym

  DOI：10.1021/jm0490890

  日期：2005.3.1

  Optimization of a high-throughput screening hit against melanin-concentrating hormone receptor 1 (MCHrl) led to the discovery of 2-(4-benzyloxy-phenyl)-N-[1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide (7a). This compound was found to be a high-affinity ligand for MCHrl and a potent inhibitor of MCH-mediated Ca2+ release, showed good plasma and CNS exposure upon oral dosing in diet-induced obese mice, and is the first reported MCHrl antagonist that is efficacious upon oral dosing in a chronic model of weight loss.(1)
• US7071182B2
  申请人：——

  公开号：US7071182B2

  公开（公告）日：2006-07-04