3-bromohexahydro-2(1H)-azocinone | 32566-61-3

• 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-bromohexahydro-2(1H)-azocinone
• 英文别名: 3-Bromoazocan-2-one
• CAS: 32566-61-3
• 化学式: C₇H₁₂BrNO
• 分子量: 206.082
• InChiKey: XWFHRFPXRGEOGA-UHFFFAOYSA-N

物化性质

• 熔点：
  163-164 °C
• 沸点：
  332.4±35.0 °C(Predicted)
• 密度：
  1.384±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 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-bromohexahydro-2(1H)-azocinone 在 palladium on activated charcoal sodium azide 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 1.5h， 生成 (S)-1-<(tert-butoxycarbonyl)methyl>-3-aminoperhydroazocin-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：

  3,3-dibromohexahydro-2(1H)-azocinone 在 palladium on activated charcoal 氢气 、 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 以88%的产率得到3-bromohexahydro-2(1H)-azocinone
  参考文献：
  名称：

  Uchikawa, Osamu; Aono, Tetsuya, Journal of Heterocyclic Chemistry, 1994, vol. 31, # 6, p. 1545 - 1552

  摘要：

  DOI：

文献信息

• In vivo Biological Activity of Antioxidative Aminothiazole Derivatives.
  作者：Osamu UCHIKAWA、Kohji FUKATSU、Masahiro SUNO、Tetsuya AONO、Takayuki DOI

  DOI：10.1248/cpb.44.2070

  日期：——

  using simple methods. Condensed 4-aminothiazoles were prepared by the reaction of alpha-bromolactams with thioamides in ethanol and 5-aminothiazole derivatives were obtained by the treatment of 3-(acylamino)lactams with a thiating agent such as phosphorous pentasulfide and Lawesson's reagent in pyridine. In vitro assay of the condensed 5-aminothiazole derivatives showed them to be potent inhibitors

  为了开发具有治疗用途的新型抗氧化剂，使用简单的方法合成了一系列新的4-和5-氨基噻唑缩合衍生物。缩合的4-氨基噻唑是通过α-溴内酰胺与硫酰胺在乙醇中的反应制得的，而5-氨基噻唑衍生物是通过用硫代试剂如五硫化二磷和Lawesson试剂在吡啶中处理3-（酰基氨基）内酰胺得到的。缩合的5-氨基噻唑衍生物的体外测定表明它们是脂质过氧化的有效抑制剂。为了在体内系统中评估这些化合物，我们设计了一种简单且可重现的方法，其中通过数值表达脊髓注射FeCl2诱导的特征行为的抑制。具有强体外活性的化合物保护中枢神经系统形成由铁依赖性脂质过氧化作用引起的损伤。结果表明，在这项研究中开发的体内测定法应可用作抗氧化剂的筛选方法，并且缩合的5-氨基噻唑衍生物是治疗中枢神经系统创伤和缺血性损伤的有希望的候选者。
• Aminothiazole derivatives.<b>I.</b>A convenient synthesis of monocyclic and condensed 5-aminothiazole derivatives
  作者：Osamu Uchikawa、Kohji Fukatsu、Tetsuya Aono

  DOI：10.1002/jhet.5570310432

  日期：1994.7

  Treatment of diamides derived from α-amino acids with phosphorus pentasulfide or Lawesson's reagent was shown to provide a convenient method to prepare 5-aminothiazoles. By this method, in addition to mono-cyclic 5-aminothiazoles 19, novel bicyclic 5-aminothiazole derivatives such as 4,5,6,7-tetrahydrothiazolo[5,4-b]pyridines 11, 5,6,7,8-tetrahydro-4H-thiazolo[5,4-b]azepines 7, 4,5,6,7,8,9-hexahydrothiazolo[5

  结果表明，用五硫化二磷或Lawesson试剂处理α-氨基酸衍生的二酰胺可为制备5-氨基噻唑提供便利的方法。通过该方法，除了单环5-氨基噻唑19，新的双环5-氨基噻唑衍生物，如4,5,6,7-四氢噻唑并[5,4- b〕吡啶11，5,6,7,8-四氢-4- ħ -噻唑并[5,4- b ]吖庚因7，-4,5,6,7,8,9- hexahydrothiazolo并[5,4- b ]吖辛因16在中等制备到从简单的良好的产率和相关的化合物双酰胺，表明该方法具有广泛的通用性。
• Bicyclic Hydantoins with a Bridgehead Nitrogen. Comparison of Anticonvulsant Activities with Binding to the Neuronal Voltage-Dependent Sodium Channel
  作者：Wayne J. Brouillette、Vladimir P. Jestkov、Milton L. Brown、M. Shamim Akhtar、Timothy M. DeLorey、George B. Brown

  DOI：10.1021/jm00046a013

  日期：1994.9

  analogous bicyclic hydantoins. However, the bicyclic hydantoins were much less potent binders to the neuronal voltage-dependent sodium channel than their monocyclic counterparts. The binding activity for the more potent bicyclic hydantoin, 1,8-diaza-9,10-dioxo-7-phenylbicyclo[5.2.1]decane (4) (IC50 = 427 microM), was comparable to that of the ring-opened, N3-methylated monocyclic hydantoin model, 5-buty

  二苯乙内酰脲（DPH或苯妥英）的抗惊厥活性与其对神经元电压依赖性钠通道的作用一致。为了进一步阐明该位点的结合要求，我们合成了几种乙内酰脲类似物，并在体外钠通道结合和/或体内全动物抗惊厥试验中对其进行了评估。5-戊基-5-苯基乙内酰脲（8）是钠通道中最有效的结合剂，具有与DPH相同的亲和力（IC50 = 40 microM），表明一个苯环足以实现良好的相互作用。由于我们先前对单苯基取代的双环2,4-恶唑烷二酮的研究表明，在恶唑烷二酮环的一面上进行N3-烷基化和5-烷基取代基的构象约束可提高活性，我们合成了两个类似的双环乙内酰脲的例子。但是，双环乙内酰脲与神经元电压依赖性钠通道的结合力远低于其单环对应物。更有效的双环乙内酰脲1,8-二氮杂-9,10-二氧杂-7-苯基双环[5.2.1]癸烷（4）的结合活性（IC50 = 427 microM）与开环的相当，N3-甲基化单环乙内酰脲模型，5-丁基-
• Substituted enantholactam derivatives as antihypertensives
  申请人：Merck & Co., Inc.

  公开号：US04396616A1

  公开（公告）日：1983-08-02

  Substituted enantholactam dipeptides and derivatives thereof are disclosed which are useful as converting enzyme inhibitors and as antihypertensives.

  本发明揭示了替代烷酰乳酸二肽及其衍生物，其可用作转化酶抑制剂和降压剂。
• Substituted enantholactam derivatives as antihypertensives, a process for preparing and a pharmaceutical composition containing them, and intermediates
  申请人：Merck & Co., Inc.

  公开号：EP0046289A2

  公开（公告）日：1982-02-24

  The invention relates to enantholactam derivatives of the formula wherein R and R4 are hydroxy, lower alkoxy, lower alkenoxy, aryloxy, diloweralkylamino lower alkoxy, hydroxy, dihydroxy, and acylamino substituted lower alkoxy, acyloxy lower alkoxy, arloweralkoxy, amino, hydroxyamino; R' is hydrogen, alkyl of from 1 to 12 carbon atoms which include branched and cyclic and unsaturated alkyl groups, substituted loweralkyl, arloweralkyl, arloweralkenyl, heteroarlower alkyl or heteroarlower alkenyl, substituted arloweralkyl, or substituted heteroarlower alkyl, or substituted heteroarlower alkenyl, wherein the aryl or heteroaryl portion is substituted, substituted arloweralkyl or substituted heteroarloweralkyl wherein the alkyl portion can be substituted, R3 is hydrogen, lower alkyl, phenyl, substituted lower alkyl; and R2 is hydrogen, lower alkyl, cycloalkyl, aminoalkyl, hydroxyalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, or heterocycloalkyl, or substituted aryl. These compounds are useful as angiotensin converting enzyme inhibitors and antihypertensives. The invention relates also to a process for preparing these compounds.

  本发明涉及式中的庚内酰胺衍生物 式中 R和R4是羟基、低级烷氧基、低级烯氧基、芳氧基、稀低级烷基氨基低级烷氧基、羟基、二羟基和酰氨基取代的低级烷氧基、酰氧基低级烷氧基、低级烷氧基、氨基、羟基氨基； R' 是氢、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、低级烷基、低级烯基、杂低级烷基或杂低级烯基、取代的低级烷基或取代的杂低级烷基或取代的杂低级烯基（其中芳基或杂芳基部分被取代）、取代的低级烷基或取代的杂低级烷基（其中烷基部分可被取代）、 R3 是氢、低级烷基、苯基、取代的低级烷基；和 R2 是氢、低级烷基、环烷基、氨基烷基、羟基烷基、芳基、杂芳基、芳烷基、杂芳烷基、杂环烷基或取代的芳基。 这些化合物可用作血管紧张素转换酶抑制剂和降压药。本发明还涉及制备这些化合物的工艺。