3,6-diethyl-N-(1-ethylpropyl)-5-(2-trifluoromethoxy-4-methoxyphenyl)pyrazin-2-amine | 355835-32-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3,6-diethyl-N-(1-ethylpropyl)-5-(2-trifluoromethoxy-4-methoxyphenyl)pyrazin-2-amine
• 英文别名: 3,6-diethyl-5-[4-methoxy-2-(trifluoromethoxy)phenyl]-N-pentan-3-ylpyrazin-2-amine
• CAS: 355835-32-4
• 化学式: C₂₁H₂₈F₃N₃O₂
• 分子量: 411.467
• InChiKey: UTJKWHBHHYMSMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氯-2,5-二乙基吡嗪 在 tris-(dibenzylideneacetone)dipalladium(0) 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 氯仿 、 水 、 甲苯 为溶剂， 反应 6.0h， 生成 3,6-diethyl-N-(1-ethylpropyl)-5-(2-trifluoromethoxy-4-methoxyphenyl)pyrazin-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

• 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：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
• [EN] SUBSTITUTED ARYLPYRAZINES<br/>[FR] ARYLPYRAZINES SUBSTITUES
  申请人：NEUROGEN CORP

  公开号：WO2001060806A2

  公开（公告）日：2001-08-23

  Arylpyrazine compounds are provided, including arylpyrazines that can bind with high affiity and high selectivity to CRF1 receptors, including human CRF1 receptors. The invention thus includes methods for treatment of disorders and diseases associated with CRF1 receptors, including CNS-related disorders and diseases, particularly affective disorders and diseases, and acute and chronic neurological disorders and diseases.
• 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.