6-tert-Butoxycarbonylamino-2-(1-carboxymethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-ylamino)-hexanoic acid | 97878-50-7

• 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: 6-tert-Butoxycarbonylamino-2-(1-carboxymethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-ylamino)-hexanoic acid
• 英文别名: (2S)-2-[[(3S)-1-(carboxymethyl)-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid
• CAS: 97878-50-7
• 化学式: C₂₃H₃₃N₃O₇
• 分子量: 463.531
• InChiKey: SWAFCAYLJAGDHL-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-tert-Butoxycarbonylamino-2-(1-carboxymethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-ylamino)-hexanoic acid 在 盐酸 、 molecular sieve 、 sodium cyanoborohydride 、 caesium carbonate 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 benzyl (2S)-6-[2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethylamino]-2-[[(3S)-2-oxo-1-(2-oxo-2-phenylmethoxyethyl)-4,5-dihydro-3H-1-benzazepin-3-yl]amino]hexanoate
  参考文献：
  名称：

  Dual Angiotensin Converting Enzyme/Thromboxane Synthase Inhibitors

  摘要：

  A variety of compounds were prepared to determine whether dual angiotensin converting enzyme (ACE)/thromboxane synthase (TxS) inhibition could be obtained in the same molecule. These compounds would be used to explore the concept that a dual inhibitor would have superior antihypertensive activity in the spontaneous hypertensive rat compared to an ACE inhibitor. Potent in vitro dual ACE and TxS inhibition was obtained in the same molecule with five series of compounds. Potent blood pressure lowering in the SHR was observed after oral administration of 8b and 11. However, a correlation between blood pressure lowering and the Al presser response inhibition was not observed. The blood pressure-lowering actions of enalapril were significantly potentiated by concurrent administration of 3, a thromboxane synthase inhibitor. Analysis of the area under the curve for 24 h showed nearly a doubling of the blood pressure-lowering effect.

  DOI：

  10.1021/jm00038a011
• 作为产物：
  描述：

  ethyl 3-amino-2,3,4,5-tetrahydro-1H-<1>benzazepin-2-one-1-acetate 在 sodium hydroxide 、 亚硝酸特丁酯 、 二丁基二氯化锡 、 sodium cyanoborohydride 、 溶剂黄146 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 26.75h， 生成 6-tert-Butoxycarbonylamino-2-(1-carboxymethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-ylamino)-hexanoic acid
  参考文献：
  名称：

  Angiotensin converting enzyme inhibitors: structure-activity profile of 1-benzazepin-2-one derivatives

  摘要：

  The preparation of a series of 3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-1-acetic acid derivatives 5a-y by reductive amination of 2,3,4,5-tetrahydro-1H-1-benzazepine-2,3-dione (7) with L-amino acid derivatives is described. The compounds were tested for inhibition of angiotensin converting enzyme. The structure-activity profile of the series is discussed. Compound 5a was especially potent when tested in dogs for inhibition of angiotensin I pressor response, having an ID50 = 0.07 mg/kg po.

  DOI：

  10.1021/jm00149a010

文献信息

• STANTON, J. L.;WATTHEY, J. W. H.;DESAI, M. N.;FINN, B. M.;BABIARZ, J. E.;+, J. MED. CHEM., 1985, 28, N 11, 1603-1606
  作者：STANTON, J. L.、WATTHEY, J. W. H.、DESAI, M. N.、FINN, B. M.、BABIARZ, J. E.、+

  DOI：——

  日期：——
• Angiotensin converting enzyme inhibitors: structure-activity profile of 1-benzazepin-2-one derivatives
  作者：James L. Stanton、Jeffrey W. H. Watthey、Mahesh N. Desai、Barbara M. Finn、Joseph E. Babiarz、Hollis C. Tomaselli

  DOI：10.1021/jm00149a010

  日期：1985.11

  The preparation of a series of 3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-1-acetic acid derivatives 5a-y by reductive amination of 2,3,4,5-tetrahydro-1H-1-benzazepine-2,3-dione (7) with L-amino acid derivatives is described. The compounds were tested for inhibition of angiotensin converting enzyme. The structure-activity profile of the series is discussed. Compound 5a was especially potent when tested in dogs for inhibition of angiotensin I pressor response, having an ID50 = 0.07 mg/kg po.
• Dual Angiotensin Converting Enzyme/Thromboxane Synthase Inhibitors
  作者：Gary M. Ksander、Mark Erion、Andrew M. Yuan、Clive G. Diefenbacher、Lena El-Chehabi、Don Cote、Nigel Levens

  DOI：10.1021/jm00038a011

  日期：1994.6

  A variety of compounds were prepared to determine whether dual angiotensin converting enzyme (ACE)/thromboxane synthase (TxS) inhibition could be obtained in the same molecule. These compounds would be used to explore the concept that a dual inhibitor would have superior antihypertensive activity in the spontaneous hypertensive rat compared to an ACE inhibitor. Potent in vitro dual ACE and TxS inhibition was obtained in the same molecule with five series of compounds. Potent blood pressure lowering in the SHR was observed after oral administration of 8b and 11. However, a correlation between blood pressure lowering and the Al presser response inhibition was not observed. The blood pressure-lowering actions of enalapril were significantly potentiated by concurrent administration of 3, a thromboxane synthase inhibitor. Analysis of the area under the curve for 24 h showed nearly a doubling of the blood pressure-lowering effect.