1-[3-(3-Azido-2-oxo-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl)-phenyl]-3-isopropyl-urea | 211761-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 1-[3-(3-Azido-2-oxo-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl)-phenyl]-3-isopropyl-urea
• 英文别名: 1-[3-[(3-azido-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl)methyl]phenyl]-3-propan-2-ylurea
• CAS: 211761-67-0
• 化学式: C₂₁H₂₄N₆O₂
• 分子量: 392.461
• InChiKey: IUSGNYRZAYUHNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[3-(3-Azido-2-oxo-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl)-phenyl]-3-isopropyl-urea 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 3.0h， 生成 1-{1-[3-(3-Isopropyl-ureido)-benzyl]-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl}-3-[1,3,4]thiadiazol-2-yl-urea
  参考文献：
  名称：

  1,3-Disubstituted Benzazepines as Novel, Potent, Selective Neuropeptide Y Y1 Receptor Antagonists

  摘要：

  A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R-1 and R-3 substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K-i values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R-1 and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R-3 in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido))benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [I-125]peptide YY (PW) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K-i = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca2+ concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.

  DOI：

  10.1021/jm990044m
• 作为产物：
  描述：

  3-氨基苯甲醇 在 氢氧化钾 、 四丁基溴化铵 、 三乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.3h， 生成 1-[3-(3-Azido-2-oxo-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl)-phenyl]-3-isopropyl-urea
  参考文献：
  名称：

  1,3-Disubstituted Benzazepines as Novel, Potent, Selective Neuropeptide Y Y1 Receptor Antagonists

  摘要：

  A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R-1 and R-3 substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K-i values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R-1 and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R-3 in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido))benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [I-125]peptide YY (PW) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K-i = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca2+ concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.

  DOI：

  10.1021/jm990044m