{3-[2-Oxo-3-(3-phenyl-ureido)-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl]-phenyl}-carbamic acid tert-butyl ester | 211760-04-2

• 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-[2-Oxo-3-(3-phenyl-ureido)-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl]-phenyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[3-[[2-oxo-3-(phenylcarbamoylamino)-4,5-dihydro-3H-1-benzazepin-1-yl]methyl]phenyl]carbamate
• CAS: 211760-04-2
• 化学式: C₂₉H₃₂N₄O₄
• 分子量: 500.597
• InChiKey: QCQCNIQTISJJJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  99.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {3-[2-Oxo-3-(3-phenyl-ureido)-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl]-phenyl}-carbamic acid tert-butyl ester 在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以100%的产率得到1-[1-(3-Amino-benzyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl]-3-phenyl-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-叠氮基-2-氧代-2,3,4,5-四氢-1H-苯并b氮杂卓 在 palladium on activated charcoal 氢氧化钾 、 四丁基溴化铵 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 {3-[2-Oxo-3-(3-phenyl-ureido)-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl]-phenyl}-carbamic acid tert-butyl ester
  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

文献信息

• 1,3-Disubstituted benzazepines as neuropeptide Y Y1 receptor antagonists
  作者：Yasushi Murakami、Sanji Hagishita、Tetsuo Okada、Makoto Kii、Hiroshi Hashizume、Tatsuroh Yagami、Masafumi Fujimoto

  DOI：10.1016/s0968-0896(99)00087-5

  日期：1999.8

  A nuclei, have been designed, synthesized, and evaluated for activity. Through a blind screening we found the compound 1-N-(3-(N'-(tert-butoxycarbonyl)amino)benzyl)-7-methoxy-(3-(3)-methylureido)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (9: IC50 = 1.6 mu M). Chemical modifications of 9 gave a potent NPY Y1 antagonist 3-(N-(4-hydroxyphenyl)-N'-methylguanidino)-1-N-(3-(N'-(tert-butoxycarbonyl)amino)benzyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (14c: IC50 = 43 nM), which had no affinity for NPY Y2 and Y5 receptors. (C) 1999 Elsevier Science Ltd. All rights reserved.
• 1,3-Disubstituted Benzazepines as Novel, Potent, Selective Neuropeptide Y Y1 Receptor Antagonists
  作者：Yasushi Murakami、Hirokazu Hara、Tetsuo Okada、Hiroshi Hashizume、Makoto Kii、Yasunobu Ishihara、Michio Ishikawa、Mayumi Shimamura、Shin-inchi Mihara、Goro Kato、Kohji Hanasaki、Sanji Hagishita、Masafumi Fujimoto

  DOI：10.1021/jm990044m

  日期：1999.7.1

  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.