NGD 98-2 | 355836-54-3

• 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: NGD 98-2
• 英文别名: 5-(2-methoxy-4-trifluoromethoxyphenyl)-[N-(1-ethyl)-propyl]-3-methoxy-6-methylpyrazine-2-amine；N-(1-ethylpropyl)-3-methoxy-5-[2-methoxy-4-(trifluoromethoxy)phenyl]-6-methylpyrazin-2-amine；3-Methoxy-5-(2-methoxy-4-(trifluoromethoxy)phenyl)-6-methyl-N-(pentan-3-yl)pyrazin-2-amine；3-methoxy-5-[2-methoxy-4-(trifluoromethoxy)phenyl]-6-methyl-N-pentan-3-ylpyrazin-2-amine
• CAS: 355836-54-3
• 化学式: C₁₉H₂₄F₃N₃O₃
• 分子量: 399.413
• InChiKey: PSUFQBRCUSJTDO-UHFFFAOYSA-N

物化性质

• 沸点：
  392.3±42.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  NGD 98-2 、 对甲苯磺酸 以 甲基叔丁基醚 、 乙酸乙酯 为溶剂， 反应 0.17h， 以89.2%的产率得到3-methoxy-5-[2-methoxy-4-(trifluoromethoxy)phenyl]-6-methyl-N-pentan-3-ylpyrazin-2-amine;4-methylbenzenesulfonic acid
  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 四(三苯基膦)钯 、 1,3-bis[(diphenylphosphino)propane]dichloronickel(II) 、 溴 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 丙醇 、 水 、 甲苯 为溶剂， 反应 47.0h， 生成 NGD 98-2
  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。
• J. Med. Chem. 2011, 54, 4187-4206
  作者：

  DOI：——

  日期：——
• 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