3,6-diethyl-N-(1-ethylpropyl)-5-[2-methoxy-4-(2-propoxy)phenyl]pyrazin-2-amine | 355835-63-1

• 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-methoxy-4-(2-propoxy)phenyl]pyrazin-2-amine
• 英文别名: 3,6-diethyl-5-(2-methoxy-4-propan-2-yloxyphenyl)-N-pentan-3-ylpyrazin-2-amine
• CAS: 355835-63-1
• 化学式: C₂₃H₃₅N₃O₂
• 分子量: 385.55
• InChiKey: GZOXBGQDEGRMNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

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-methoxy-4-(2-propoxy)phenyl]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

• 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.