3-carboxy-1-N-(3-(N'-(3-isopropylureido))benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one | 239097-60-0

• 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: 3-carboxy-1-N-(3-(N'-(3-isopropylureido))benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
• 英文别名: 2-oxo-1-[[3-(propan-2-ylcarbamoylamino)phenyl]methyl]-4,5-dihydro-3H-1-benzazepine-3-carboxylic acid
• CAS: 239097-60-0
• 化学式: C₂₂H₂₅N₃O₄
• 分子量: 395.458
• InChiKey: UCUMUFWYFWFQBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  98.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  苯胺 、 3-carboxy-1-N-(3-(N'-(3-isopropylureido))benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one 在 1-(3-(dimethylamino)propyl)-3-ethoxycarbonyldiimide hydrochloride 、 1-羟基苯并三唑 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以47%的产率得到3-(anilinocarbonyl)-1-N-(3-(N'-(3-isopropylureido)benzyl))-2,3,4,5-tetrahydro-1H-1-benazepin-2-one
  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-氯-1,3,4,5-四氢-2H-1-苯并氮杂卓-2-酮 在 盐酸 、 氢氧化钾 、 sodium hydroxide 、 四丁基溴化铵 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 63.33h， 生成 3-carboxy-1-N-(3-(N'-(3-isopropylureido))benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one
  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