(3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyloxycarbonylamino)ectic acid ethyl ester | 195510-97-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyloxycarbonylamino)ectic acid ethyl ester
• CAS: 195510-97-5
• 化学式: C₃₀H₃₁N₅O₇
• 分子量: 573.605
• InChiKey: HQXUULYIWJZKQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  42.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  147.66
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  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 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 (3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyloxycarbonylamino)ectic acid
  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：

  1,3-dihydro-1-methyl-3-amino-5-(3-methoxyphenyl)-2H-1,4-benzodiazepine-2-one 、 (3-Isocyanato-benzyloxycarbonylamino)-acetic acid ethyl ester 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (3-{3-[5-(3-methoylphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]ureido}benzyloxycarbonylamino)ectic acid ethyl 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