3-methoxy-[N-(1-ethyl)propyl]-5-bromo-6-methylpyrazine-2-amine | 848949-09-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-methoxy-[N-(1-ethyl)propyl]-5-bromo-6-methylpyrazine-2-amine
• 英文别名: (5-bromo-3-methoxy-6-methyl-pyrazin-2-yl)-(1-ethyl-propyl)-amine；5-bromo-3-methoxy-6-methyl-N-pentan-3-ylpyrazin-2-amine
• CAS: 848949-09-7
• 化学式: C₁₁H₁₈BrN₃O
• 分子量: 288.187
• InChiKey: RSWILCOQDPKRNL-UHFFFAOYSA-N

物化性质

• 沸点：
  317.9±42.0 °C(Predicted)
• 密度：
  1.320±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-methoxy-[N-(1-ethyl)propyl]-5-bromo-6-methylpyrazine-2-amine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 potassium acetate 、 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 96.0h， 生成 (1-ethyl-propyl)-{5-[3-(1-ethyl-propyl)-1,5-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl]-3-methoxy-6-methyl-pyrazin-2-yl}-amine
  参考文献：
  名称：

  5-Aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds

  摘要：

  5-芳基吡唑并[4,3-d]嘧啶，6-芳基吡唑并[3,4-d]嘧啶及相关化合物，以及其他化学相关化合物，作为CRF 1受体的选择性调节剂。这些化合物在治疗多种中枢神经系统和外周障碍，特别是压力、焦虑、抑郁、心血管障碍和进食障碍方面具有用途。还提供了治疗这些障碍的方法以及包装的药物组合物。本发明的化合物还可用作CRF受体定位的探针和CRF受体结合测定中的标准。给出了在受体定位研究中使用这些化合物的方法。

  公开号：

  US20050070542A1
• 作为产物：
  描述：

  3-氨基戊烷 在 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) 、 溴 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 丙醇 为溶剂， 反应 35.0h， 生成 3-methoxy-[N-(1-ethyl)propyl]-5-bromo-6-methylpyrazine-2-amine
  参考文献：
  名称：

  Discovery of N-(1-Ethylpropyl)-[3-methoxy-5-(2-methoxy-4-trifluoromethoxyphenyl)-6-methyl-pyrazin-2-yl]amine 59 (NGD 98−2): An Orally Active Corticotropin Releasing Factor-1 (CRF-1) Receptor Antagonist

  摘要：

  The design, synthesis, and structure-activity relationships of a novel series of pyrazines, acting as corticotropin releasing factor-1 (CRF-1) receptor antagonists, are described. Synthetic methodologies were developed to prepare a number of substituted pyrazine cores utilizing regioselective halogenation and chemoselective derivatization. Noteworthy, an efficient 5-step synthesis was developed for the lead compound 59 (NGD 98-2), which required no chromatography. Compound 59 was characterized as an orally bioavailable, brain penetrant, and highly selective CRF-1 receptor antagonist. Occupancy of rat brain CRF-1 receptors was quantified using ex vivo receptor occupancy assays, using both brain tissue homogenates as well as brain slices receptor autoradiography. Behaviorally, oral administration of 59 significantly antagonized CRF-induced locomotor activity at doses as low as 10 mg/kg and dose-dependently reduced the restraint stress-induced ACTH increases.

  DOI：

  10.1021/jm200365y

文献信息

• J. Med. Chem. 2011, 54, 4187-4206
  作者：

  DOI：——

  日期：——
• 5-ARYL-PYRAZOLO [4,3-D] PYRIMIDINES, PYRIDINES, AND PYRAZINES AND RELATED COMPOUNDS
  申请人：NEUROGEN CORPORATION

  公开号：EP1675858A2

  公开（公告）日：2006-07-05
• [EN] 5-ARYL-PYRAZOLO[4,3-D]PYRIMIDINES, PYRIDINES, AND PYRAZINES AND RELATED COMPOUNDS<br/>[FR] 5-ARYL-PYRAZOLO[4,3-D]PYRIMIDINES, PYRIDINES, ET PYRAZINES ET COMPOSES ASSOCIES
  申请人：NEUROGEN CORP

  公开号：WO2005028480A2

  公开（公告）日：2005-03-31

  5-aryl-Pyrazolo[4,3-d] pyrimidines, 6-aryl-Pyrazolo[3,4-d]pyrimidines and related compounds, as well as other chemically related compounds, that act as selective modulators of CRF 1 receptors are provided. These compounds are useful in the treatment of a number of CNS and periphereal disorders, particularly stress, anxiety, depression, cardiovascular disorders, and eating disorders. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of CRF receptors and as standards in assays for CRIF receptor binding. Methods of using the compounds in receptor localization studies are given.
• 5-Aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds
  申请人：Hodgetts J. Kevin

  公开号：US20050070542A1

  公开（公告）日：2005-03-31

  5-aryl-Pyrazolo[4,3-d]pyrimidines, 6-aryl-Pyrazolo[3,4-d]pyrimidines and related compounds, as well as other chemically related compounds, that act as selective modulators of CRF 1 receptors are provided. These compounds are useful in the treatment of a number of CNS and periphereal disorders, particularly stress, anxiety, depression, cardiovascular disorders, and eating disorders. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of CRF receptors and as standards in assays for CRF receptor binding. Methods of using the compounds in receptor localization studies are given.

  5-芳基吡唑并[4,3-d]嘧啶，6-芳基吡唑并[3,4-d]嘧啶及相关化合物，以及其他化学相关化合物，作为CRF 1受体的选择性调节剂。这些化合物在治疗多种中枢神经系统和外周障碍，特别是压力、焦虑、抑郁、心血管障碍和进食障碍方面具有用途。还提供了治疗这些障碍的方法以及包装的药物组合物。本发明的化合物还可用作CRF受体定位的探针和CRF受体结合测定中的标准。给出了在受体定位研究中使用这些化合物的方法。
• Discovery of <i>N</i>-(1-Ethylpropyl)-[3-methoxy-5-(2-methoxy-4-trifluoromethoxyphenyl)-6-methyl-pyrazin-2-yl]amine <b>59</b> (NGD 98−2): An Orally Active Corticotropin Releasing Factor-1 (CRF-1) Receptor Antagonist
  作者：Kevin J. Hodgetts、Ping Ge、Taeyoung Yoon、Stéphane De Lombaert、Robbin Brodbeck、Michael Gulianello、Andrzej Kieltyka、Raymond F. Horvath、John H. Kehne、James E. Krause、George D. Maynard、Diane Hoffman、Younglim Lee、Laurence Fung、Dario Doller

  DOI：10.1021/jm200365y

  日期：2011.6.23

  The design, synthesis, and structure-activity relationships of a novel series of pyrazines, acting as corticotropin releasing factor-1 (CRF-1) receptor antagonists, are described. Synthetic methodologies were developed to prepare a number of substituted pyrazine cores utilizing regioselective halogenation and chemoselective derivatization. Noteworthy, an efficient 5-step synthesis was developed for the lead compound 59 (NGD 98-2), which required no chromatography. Compound 59 was characterized as an orally bioavailable, brain penetrant, and highly selective CRF-1 receptor antagonist. Occupancy of rat brain CRF-1 receptors was quantified using ex vivo receptor occupancy assays, using both brain tissue homogenates as well as brain slices receptor autoradiography. Behaviorally, oral administration of 59 significantly antagonized CRF-induced locomotor activity at doses as low as 10 mg/kg and dose-dependently reduced the restraint stress-induced ACTH increases.