tert-butyl [2-(2-phenyl-7,8-dihydro-1H-furo[3,2-e]benzimidazol-1-yl)ethyl]carbamate | 1309752-66-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: tert-butyl [2-(2-phenyl-7,8-dihydro-1H-furo[3,2-e]benzimidazol-1-yl)ethyl]carbamate
• 英文别名: tert-butyl N-[2-(2-phenyl-7,8-dihydrofuro[2,3-g]benzimidazol-1-yl)ethyl]carbamate
• CAS: 1309752-66-6
• 化学式: C₂₂H₂₅N₃O₃
• 分子量: 379.459
• InChiKey: JSQILEGXTIEKDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl [2-(2-phenyl-7,8-dihydro-1H-furo[3,2-e]benzimidazol-1-yl)ethyl]carbamate 在 盐酸 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 0.33h， 以98%的产率得到2-(2-phenyl-7,8-dihydro-1H-furo[3,2-e]benzimidazol-1-yl)ethanamine dihydrochloride
  参考文献：
  名称：

  Synthesis of a Novel Series of Tricyclic Dihydrofuran Derivatives: Discovery of 8,9-Dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridines as Melatonin Receptor (MT₁/MT₂) Ligands

  摘要：

  Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan la. By screening the central tricyclic cores, we identified 8,9-dihydrofuro [3,2-c]pyrazolo [1,5-a]pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, K-i = 0.062 nM; MT2, K-i = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.

  DOI：

  10.1021/jm200385u
• 作为产物：
  描述：

  2,6-二氟苯乙酸 在 lithium aluminium tetrahydride 、 lithium hydroxide monohydrate 、 硫酸 、 palladium 10% on activated carbon 、 水 、 氢气 、 硝酸 、 potassium carbonate 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.5h， 生成 tert-butyl [2-(2-phenyl-7,8-dihydro-1H-furo[3,2-e]benzimidazol-1-yl)ethyl]carbamate
  参考文献：
  名称：

  Synthesis of a Novel Series of Tricyclic Dihydrofuran Derivatives: Discovery of 8,9-Dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridines as Melatonin Receptor (MT₁/MT₂) Ligands

  摘要：

  Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan la. By screening the central tricyclic cores, we identified 8,9-dihydrofuro [3,2-c]pyrazolo [1,5-a]pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, K-i = 0.062 nM; MT2, K-i = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.

  DOI：

  10.1021/jm200385u

文献信息

• Synthesis of a Novel Series of Tricyclic Dihydrofuran Derivatives: Discovery of 8,9-Dihydrofuro[3,2-<i>c</i>]pyrazolo[1,5-<i>a</i>]pyridines as Melatonin Receptor (MT₁/MT₂) Ligands
  作者：Tatsuki Koike、Takafumi Takai、Yasutaka Hoashi、Masaharu Nakayama、Yohei Kosugi、Masato Nakashima、Shin-ichi Yoshikubo、Keisuke Hirai、Osamu Uchikawa

  DOI：10.1021/jm200385u

  日期：2011.6.23

  Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan la. By screening the central tricyclic cores, we identified 8,9-dihydrofuro [3,2-c]pyrazolo [1,5-a]pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, K-i = 0.062 nM; MT2, K-i = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.