({2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]ethylcarbamoyl}methyl)carbamic acid 3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyl ester | 195510-99-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: ({2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]ethylcarbamoyl}methyl)carbamic acid 3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyl ester
• CAS: 195510-99-7
• 化学式: C₄₆H₅₄N₈O₈
• 分子量: 846.984
• InChiKey: TXPVKTSKNPQKQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.96
• 重原子数：
  62.0
• 可旋转键数：
  18.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  192.03
• 氢给体数：
  5.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  ({2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]ethylcarbamoyl}methyl)carbamic acid 3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyl ester 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以40%的产率得到({2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]ethylcarbamoyl}methyl)carbamic acid 3-{3-[5-(3-hydroxyphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyl ester
  参考文献：
  名称：

  Synthesis and structure-activity relationships of dual histamine H2 and gastrin receptor antagonists with decreased hydrophobicity

  摘要：

  In order to study structure-activity relationships of the previously reported dual histamine H-2 and gastrin receptor antagonists and also to improve their low oral absorbability, we tried two chemical modifications. One tried to decrease the high hydrophobicity of the parent hybrid compounds to an appropriate level by incorporating a hydrophilic group into the molecule and the other by replacing the more hydrophobic groups with less hydrophobic ones. The former compounds (type I) involved hybrid compounds with a hydroxyl group at a position of a spacer, a piperidine moiety of H(2)A, or a phenyl ring at the C-5 of the benzodiazepine skeleton as well as those with a free carboxyl group in the piperidine moiety of H(2)A. The latter (type II) involved hybrid compounds with the C-5-phenyl group replaced with either a methyl group or hydrogen atom. Among them, only a type I compound, ({2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]ethylcarbamoyl}methyl)carbamic acid 3-{3-[5-(3-hydroxyphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyl ester (18), showed potent dual histamine H-2 and gastrin receptor antagonistic activity, whereas others resulted in a significant decrease of histamine H-2 receptor antagonistic activity. The in vivo gastric acid antisecretory activity of 18 evaluated by Schild's rat method, however, did not suggest any notable improvement in oral absorbability. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00074-6
• 作为产物：
  描述：

  (3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyloxycarbonylamino)ectic acid ethyl ester 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 ({2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]ethylcarbamoyl}methyl)carbamic acid 3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyl ester
  参考文献：
  名称：

  Synthesis and structure-activity relationships of dual histamine H2 and gastrin receptor antagonists with decreased hydrophobicity

  摘要：

  In order to study structure-activity relationships of the previously reported dual histamine H-2 and gastrin receptor antagonists and also to improve their low oral absorbability, we tried two chemical modifications. One tried to decrease the high hydrophobicity of the parent hybrid compounds to an appropriate level by incorporating a hydrophilic group into the molecule and the other by replacing the more hydrophobic groups with less hydrophobic ones. The former compounds (type I) involved hybrid compounds with a hydroxyl group at a position of a spacer, a piperidine moiety of H(2)A, or a phenyl ring at the C-5 of the benzodiazepine skeleton as well as those with a free carboxyl group in the piperidine moiety of H(2)A. The latter (type II) involved hybrid compounds with the C-5-phenyl group replaced with either a methyl group or hydrogen atom. Among them, only a type I compound, ({2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]ethylcarbamoyl}methyl)carbamic acid 3-{3-[5-(3-hydroxyphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyl ester (18), showed potent dual histamine H-2 and gastrin receptor antagonistic activity, whereas others resulted in a significant decrease of histamine H-2 receptor antagonistic activity. The in vivo gastric acid antisecretory activity of 18 evaluated by Schild's rat method, however, did not suggest any notable improvement in oral absorbability. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00074-6