5-(2,4-dichlorophenyl)-6-ethyl-[N-(1-ethyl)propyl]pyrazine-2-amine | 355835-13-1

• 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: 5-(2,4-dichlorophenyl)-6-ethyl-[N-(1-ethyl)propyl]pyrazine-2-amine
• 英文别名: 5-(2,4-dichlorophenyl)-6-ethyl-N-pentan-3-ylpyrazin-2-amine
• CAS: 355835-13-1
• 化学式: C₁₇H₂₁Cl₂N₃
• 分子量: 338.28
• InChiKey: LWGSVRCYJDVBSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(2,4-dichlorophenyl)-6-ethyl-[N-(1-ethyl)propyl]pyrazine-2-amine 在 N-溴代丁二酰亚胺(NBS) 、 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 4.0h， 生成 5-(2,4-dichlorophenyl)-6-ethyl-[N-(1-ethyl)propyl]-3-butylpyrazine-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
• 作为产物：
  描述：

  3-氨基戊烷 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 丙醇 、 乙二醇二甲醚 、 氯仿 、 水 为溶剂， 反应 31.0h， 生成 5-(2,4-dichlorophenyl)-6-ethyl-[N-(1-ethyl)propyl]pyrazine-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

• [EN] 5-SUBSTITUTED-2-ARYLPYRAZINES AS MODULATORS OF CRF RECEPTORS<br/>[FR] 2-ARYLPYRAZINES SUBSTITUEES EN 5 COMME MODULATEURS SUR LES RECEPTEURS CRF
  申请人：NEUROGEN CORP

  公开号：WO2004018437A1

  公开（公告）日：2004-03-04

  Novel 5-substituted-2-arylpyrazine compounds are provided. Such compounds can act as selective modulators of CRF receptors. The 5-substituted-2-arylpyrazine compounds provided herein are useful in the treatment of a number of CNS and peripheral 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 provided 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.

  提供了一种新型的5-取代-2-芳基吡嗪化合物。这些化合物可以作为CRF受体的选择性调节剂。本文提供的5-取代-2-芳基吡嗪化合物在治疗多种中枢神经系统和外周疾病方面具有用途，特别是压力、焦虑、抑郁、心血管疾病和进食障碍。还提供了治疗这些疾病的方法以及包装的药物组合物。提供的化合物还可用作CRF受体的定位探针和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。
• Substituted arylpyrazines
  申请人：——

  公开号：US20030018035A1

  公开（公告）日：2003-01-23

  Arylpyrazine compounds are provided, including arylpyrazines that can bind with high affinity and high selectivity to CRF 1 receptors, including human CRF 1 receptors. The invention thus includes methods for treatment of disorders and diseases associated with CRF 1 receptors, including CNS-related disorders and diseases, particularly affective disorders and diseases, and acute and chronic neurological disorders and diseases.

  提供了芳基吡嗪化合物，包括可以与CRF1受体结合并具有高亲和力和高选择性的芳基吡嗪，包括人类CRF1受体。因此，该发明涉及用于治疗与CRF1受体相关的疾病和疾病的方法，包括与中枢神经系统相关的疾病和疾病，特别是情感障碍和疾病以及急性和慢性神经系统疾病。
• 5-Substituted-2-arylpyrazines
  申请人：Neurogen Corporation

  公开号：US20040106620A1

  公开（公告）日：2004-06-03

  Novel 5-substituted-2-arylpyrazine compounds are provided. Such compounds can act as selective modulators of CRF receptors. The 5-substituted-2-arylpyrazine compounds provided herein 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 provided 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.

  本文提供了一种新型的5-取代-2-芳基吡嗪化合物。这些化合物可以作为选择性CRF受体调节剂。本文提供的5-取代-2-芳基吡嗪化合物在治疗多种中枢神经系统和外周疾病方面具有用途，尤其是在应对压力、焦虑、抑郁、心血管疾病和进食障碍方面。此外，还提供了治疗这些疾病的方法和包装的药物组合物。这些化合物还可用作CRF受体定位的探针和CRF受体结合测定的标准。本文还提供了使用这些化合物进行受体定位研究的方法。
• Substituted Arylpyrazines
  申请人：Yoon Taeyoung

  公开号：US20070225287A1

  公开（公告）日：2007-09-27

  Arylpyrazine compounds are provided, including arylpyrazines that can bind with high affinity and high selectivity to CRF 1 receptors, including human CRF 1 receptors. The invention thus includes methods for treatment of disorders and diseases associated with CRF 1 receptors, including CNS-related disorders and diseases, particularly affective disorders and diseases, and acute and chronic neurological disorders and diseases.

  提供了芳基吡嗪类化合物，其中包括能够与CRF1受体高亲和力和高选择性结合的芳基吡嗪，包括人类CRF1受体。因此，本发明包括用于治疗与CRF1受体相关的疾病和疾病的方法，包括与中枢神经系统相关的疾病和疾病，特别是情感障碍和疾病，以及急性和慢性神经系统疾病和疾病。
• SUBSTITUTED ARYLPYRAZINES
  申请人：NEUROGEN CORPORATION

  公开号：EP1255740B1

  公开（公告）日：2005-10-19