3,6-diethyl-2-(1-ethylpropoxy)-5-(2,4-dichlorophenyl)pyrazine | 355835-95-9

• 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: 3,6-diethyl-2-(1-ethylpropoxy)-5-(2,4-dichlorophenyl)pyrazine
• 英文别名: 2-(2,4-Dichlorophenyl)-3,6-diethyl-5-pentan-3-yloxypyrazine
• CAS: 355835-95-9
• 化学式: C₁₉H₂₄Cl₂N₂O
• 分子量: 367.318
• InChiKey: XFFQPEYVHSNGRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氯-2,5-二乙基吡嗪 在 四(三苯基膦)钯 、 sodium hydride 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 10.25h， 生成 3,6-diethyl-2-(1-ethylpropoxy)-5-(2,4-dichlorophenyl)pyrazine
  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

• 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。
• 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：EP1255740A2

  公开（公告）日：2002-11-13
• US6995161B2
  申请人：——

  公开号：US6995161B2

  公开（公告）日：2006-02-07
• US7202250B2
  申请人：——

  公开号：US7202250B2

  公开（公告）日：2007-04-10