1-<(tert-butoxycarbonyl)methyl>-3-aminoperhydroazepin-2-one | 105433-98-5

• 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: 1-<(tert-butoxycarbonyl)methyl>-3-aminoperhydroazepin-2-one
• 英文别名: Tert-butyl 2-(3-amino-2-oxoazepan-1-yl)acetate
• CAS: 105433-98-5
• 化学式: C₁₂H₂₂N₂O₃
• 分子量: 242.318
• InChiKey: MLOSYSBYXDSKHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<(tert-butoxycarbonyl)methyl>-3-aminoperhydroazepin-2-one 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 2.0h， 生成 (carboxymethyl)-3-<(1-carboxy-3-phenylpropyl)amino>perhydroazepin-2-one
  参考文献：
  名称：

  Conformationally restricted inhibitors of angiotensin-converting enzyme. Synthesis and computations

  摘要：

  A series of inhibitors of angiotensin converting enzyme (ACE, dipeptidyl carboxypeptidase, EC 3.4.15.1) is described which addresses certain conformational aspects of the enzyme-inhibitor interaction. In this study the alanylproline portion of the potent ACE inhibitor enalaprilat (2) is replaced by a series of monocyclic lactams containing the required recognition and binding elements. In order to more fully assess the lactam ring conformations and the key backbone angle psi as defined in 3 with respect to possible enzyme-bound conformations, a series of model lactams was investigated with use of molecular mechanics. The results point to a correlation between inhibitor potency (IC50) and the computed psi angle for the lowest energy conformation of the model compounds. Thus the psi angle as defined in 3 is an important determinant in the binding of inhibitors to ACE. The inhibition data in conjunction with the computational data have served to define a window of psi angles from 130 degrees to 170 degrees which seems to be acceptable to the ACE active site.

  DOI：

  10.1021/jm00152a014
• 作为产物：
  描述：

  碘乙酸叔丁酯 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 1-<(tert-butoxycarbonyl)methyl>-3-aminoperhydroazepin-2-one
  参考文献：
  名称：

  Conformationally restricted inhibitors of angiotensin-converting enzyme. Synthesis and computations

  摘要：

  A series of inhibitors of angiotensin converting enzyme (ACE, dipeptidyl carboxypeptidase, EC 3.4.15.1) is described which addresses certain conformational aspects of the enzyme-inhibitor interaction. In this study the alanylproline portion of the potent ACE inhibitor enalaprilat (2) is replaced by a series of monocyclic lactams containing the required recognition and binding elements. In order to more fully assess the lactam ring conformations and the key backbone angle psi as defined in 3 with respect to possible enzyme-bound conformations, a series of model lactams was investigated with use of molecular mechanics. The results point to a correlation between inhibitor potency (IC50) and the computed psi angle for the lowest energy conformation of the model compounds. Thus the psi angle as defined in 3 is an important determinant in the binding of inhibitors to ACE. The inhibition data in conjunction with the computational data have served to define a window of psi angles from 130 degrees to 170 degrees which seems to be acceptable to the ACE active site.

  DOI：

  10.1021/jm00152a014

文献信息

• Lactams and bicyclic lactams useful as cholecystokinin antagonists
  申请人：Merck & Co., Inc.

  公开号：US04757068A1

  公开（公告）日：1988-07-12

  This invention relates to lactams, bicyclic lactams and related compounds which are useful as cholecystokinin antagonists.

  该发明涉及乳内酰胺，双环乳内酰胺及相关化合物，它们可用作胆囊收缩素拮抗剂。
• US4757068A
  申请人：——

  公开号：US4757068A

  公开（公告）日：1988-07-12
• Conformationally restricted inhibitors of angiotensin-converting enzyme. Synthesis and computations
  作者：Eugene D. Thorsett、Elbert E. Harris、Susan D. Aster、Elwood R. Peterson、James P. Snyder、James P. Springer、Jordan Hirshfield、Edward W. Tristram、Arthur A. Patchett

  DOI：10.1021/jm00152a014

  日期：1986.2

  A series of inhibitors of angiotensin converting enzyme (ACE, dipeptidyl carboxypeptidase, EC 3.4.15.1) is described which addresses certain conformational aspects of the enzyme-inhibitor interaction. In this study the alanylproline portion of the potent ACE inhibitor enalaprilat (2) is replaced by a series of monocyclic lactams containing the required recognition and binding elements. In order to more fully assess the lactam ring conformations and the key backbone angle psi as defined in 3 with respect to possible enzyme-bound conformations, a series of model lactams was investigated with use of molecular mechanics. The results point to a correlation between inhibitor potency (IC50) and the computed psi angle for the lowest energy conformation of the model compounds. Thus the psi angle as defined in 3 is an important determinant in the binding of inhibitors to ACE. The inhibition data in conjunction with the computational data have served to define a window of psi angles from 130 degrees to 170 degrees which seems to be acceptable to the ACE active site.