3-bromoperhydroazonin-2-one | 32566-65-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 3-bromoperhydroazonin-2-one
• 英文别名: (+/-)-3-Brom-octahydro-azonin-2-on；3-bromo-azonan-2-one；3-bromooctahydro-2H-azonin-2-one；3-bromoazonan-2-one
• CAS: 32566-65-7
• 化学式: C₈H₁₄BrNO
• 分子量: 220.109
• InChiKey: YGWOBAFUBQDCKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-bromoperhydroazonin-2-one 在 palladium on activated charcoal 叠氮化锂 、 氢气 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0~80.0 ℃ 、275.79 kPa 条件下， 反应 99.5h， 生成 (S)-2-((S)-1-Carboxymethyl-2-oxo-azonan-3-ylamino)-4-phenyl-butyric acid ethyl ester; compound with trifluoro-acetic acid
  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

• Substituted caprylolactam derivatives as anti-hypertensives
  申请人：Merck & Co., Inc.

  公开号：US04587238A1

  公开（公告）日：1986-05-06

  The invention in its broad aspects relates to caprylolactam derivatives which are useful as angiotensin converting enzyme inhibitors and as antihypertensives.

  这项发明从广义上讲涉及到辛酰乳酰胺衍生物，这些衍生物可用作血管紧张素转化酶抑制剂和降压药。
• Substituted caprylolactam derivatives as antihypertensives, process for preparing and pharmaceutical composition comprising them
  申请人：Merck & Co., Inc.

  公开号：EP0046292A1

  公开（公告）日：1982-02-24

  The invention relates to caprylolactam derivatives of the formula: wherein R and R3 are hydroxy, lower alkoxy, lower alkenoxy, aryloxy, arloweralkoxy; hydrogen, alkyl of from 1 to 12 carbon atoms which include branched and cyclic and unsaturated alkyl groups, substituted loweralkyl wherein the substituent(s) can be halo, lower alkoxy, hydroxy, aryloxy, amino, loweralkylamino, aminoloweralkylthio, aminoloweralkoxy, diloweralkylamino, acylamino, arylamino, guanidino, phthalimido, mercapto, loweralkylthio, arylthio, carboxy, carboxamido or carboloweralkoxy, arloweralkyl, arloweralkenyl, heteroarlower alkyl or heteroarlower alkenyl, substituted arloweralkyl, or substituted heteroarlower alkyl, or substituted heteroarlower alkenyl, wherein the aryl or heteroaryl substituents are halo, dihalo, lower alkyl, hydroxy, lower alkoxy, amino, aminomethyl, phenyloxy, acylamino, diloweralkylamino, loweralkylamino, carboxyl, haloloweralkyl, acyl or aroyl; arloweralkyl or heteroarloweralkyl substituted on the alkyl portion by amino, hydroxyl or acylamino; R2 and R are hydrogen or lower alkyl; and the pharmaceutically acceptable salts thereof and a process for preparing them. Those compounds are useful as angiotensin converting enzyme inhibitors and as antihypertensives.

  本发明涉及式如下的辛酰内酰胺衍生物： 式中 R和R3是羟基 低级烷氧基 低级烯氧基 芳氧基 低级烷氧基 氢、 1 至 12 个碳原子的烷基，包括支链、环状和不饱和烷基、 取代的低级烷基，其中的取代基可以是卤代、低级烷氧基、羟基、芳氧基、氨基、低级烷基氨基、氨醇低级烷硫基、氨醇低级烷氧基、稀释低级烷基氨基、酰基氨基、芳基氨基、胍基、酞酰亚胺基、巯基、低级烷硫基、芳基硫基、羧基、羧酰胺基或碳醇低级烷氧基、 低级烷基、低级烯基、杂低级烷基或杂低级烯基、 取代的芳基或杂芳基，其中芳基或杂芳基取代基为卤代、二卤代、低级烷基、羟基、低级烷氧基、氨基、氨甲基、苯氧基、酰氨基、稀低级烷基氨基、低级烷基氨基、羧基、卤代低级烷基、酰基或芳基； 烷基部分被氨基、羟基或酰基氨基取代的低级烷基或杂芳低级烷基； R2 和 R 是氢或低级烷基； 及其药学上可接受的盐类和制备方法。这些化合物可用作血管紧张素转换酶抑制剂和降压药。
• HARRIS, E. E.;PATCHETT, A. A.;THORSETT, E. D.
  作者：HARRIS, E. E.、PATCHETT, A. A.、THORSETT, E. D.

  DOI：——

  日期：——
• US4587238A
  申请人：——

  公开号：US4587238A

  公开（公告）日：1986-05-06
• 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.