2-吖丁啶酮,4-(乙酰氧基)-3,3-二乙基- | 126997-07-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: 2-吖丁啶酮,4-(乙酰氧基)-3,3-二乙基-
• 英文名称: 3,3-diethyl-4-acetoxyazetidin-2-one
• 英文别名: 4-oxo-3,3-diethylazetidin-2-yl acetate；3,3-diethyl-4-acetyloxy-azetidin-2-one；2-acetoxy-3,3-diethyl-4-oxo-azetidine；4-acetyloxy-3,3-diethylazetidin-2-one；(R,S)-2-acetoxy-3,3-diethyl-azetidin-4-one；2-acetoxy-3,3-diethyl-azetidin-4-one；4-acetoxy-3,3-diethyl-2-azetidinone；2-Azetidinone, 4-(acetyloxy)-3,3-diethyl-；(3,3-diethyl-4-oxoazetidin-2-yl) acetate
• CAS: 126997-07-7
• 化学式: C₉H₁₅NO₃
• 分子量: 185.223
• InChiKey: METIWGORERLVOW-UHFFFAOYSA-N

物化性质

• 沸点：
  307.4±35.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-吖丁啶酮,4-(乙酰氧基)-3,3-二乙基- 在 镍 4-二甲氨基吡啶 、 氢气 、 溶剂黄146 、 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 丙酮 、 叔丁醇 为溶剂， 反应 26.5h， 生成 4-<(4-carboxyphenyl)oxy>-3,3-diethyl-1-<<<<4-(dimethylamino)phenyl>methyl>amino>carbonyl>-2-azetidinone
  参考文献：
  名称：

  Orally active .beta.-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones

  摘要：

  A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1-[[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.

  DOI：

  10.1021/jm00099a003
• 作为产物：
  描述：

  2-乙基丁醛 在 sodium acetate 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 2-吖丁啶酮,4-(乙酰氧基)-3,3-二乙基-
  参考文献：
  名称：

  Orally active .beta.-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones

  摘要：

  A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1-[[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.

  DOI：

  10.1021/jm00099a003

文献信息

• Orally active .beta.-lactam inhibitors of human leukocyte elastase. 2. Effect of C-4 substitution
  作者：William K. Hagmann、Amy L. Kissinger、Shrenik K. Shah、Paul E. Finke、Conrad P. Dorn、Karen A. Brause、Bonnie M. Ashe、Hazel Weston、Alan L. Maycock

  DOI：10.1021/jm00058a015

  日期：1993.3

  concern. Fortunately, compounds containing 4-hydroxybenzoic acid and 4-hydroxyphenylacetic acid ethers at C-4 were among the most active analogs. These phenolic acids are also found as urinary metabolites in healthy humans. Other heteroaryls at C-4 were also orally active in this model despite relatively modest enzyme activity.

  探索了改变3,3-二乙基-1-[（（苄氨基）羰基] -2-氮杂环丁酮的C-4取代基对HLE的抑制作用以及在HLE诱导的仓鼠肺损伤模型中的作用。在最有效的化合物中，k（obs）/ [I] = 6900 M-1 s-1的化合物在该位置的取代物似乎不与HLE强烈相互作用。但是，该位置的取代基对体内活性具有显着影响。用C-4芳基羧酸醚（在30 mg / kg po时抑制60-85％）实现了肺出血试验中最大的口服活性。基于这些化合物所建立的抑制机理，C-4取代基将被释放，因此，这些C-4取代基的药理学潜力受到极大关注。幸好，在C-4处含有4-羟基苯甲酸和4-羟基苯基乙酸醚的化合物是活性最高的类似物。这些酚酸也被发现是健康人的尿中代谢产物。尽管该酶活性相对适中，但在该模型中C-4处的其他杂芳基也具有口服活性。
• Design, Synthesis and Stability of N-Acyloxymethyl- and N-Aminocarbonyloxymethyl-2-azetidinones as Human Leukocyte Elastase Inhibitors
  作者：A Clemente、A Domingos、A.P Grancho、J Iley、R Moreira、J Neres、N Palma、A.B Santana、E Valente

  DOI：10.1016/s0960-894x(01)00131-7

  日期：2001.4

  N-acyloxymethyl- and N-aminocarbonyloxymethyl derivatives of 2-azetidinones, 3, with different substituent patterns at the beta-lactam C-3 and C-4 positions, were designed as potential mechanism-based inhibitors for human leukocyte elastase and found to exhibit inhibitory potency and selectivity for the enzyme.

  设计了一系列一系列2-氮杂环丁烷酮的N-酰氧基甲基-和N-氨基羰基氧基甲基衍生物3，它们在β-内酰胺C-3和C-4位置具有不同的取代基图案，被认为是潜在的基于机制的人白细胞弹性蛋白酶抑制剂。被发现对酶具有抑制力和选择性。
• Substituted azetidinones as anti-inflammatory and antidegenerative agents
  申请人：Merck & Co., Inc.

  公开号：US05952321A1

  公开（公告）日：1999-09-14

  New substituted azetidinones of the general Formula (I) which have been found to be potent elastase inhibitors and thereby useful anti-inflammatory and antidegenerative agents are described, wherein n is

  一种新的替代性氮杂环丁酮，具有通用公式（I），已被发现为有效的弹性蛋白酶抑制剂，因此可用作抗炎和抗退行性药物，其中n是。
• .beta.-lactams useful in determining the amount of elastase in a
  申请人：Merck & Co., Inc.

  公开号：US05229510A1

  公开（公告）日：1993-07-20

  Disclosed are .beta.-lactams of formula I ##STR1## wherein X is a chromogenic or fluorogenic substituted aryl or heteroaryl, which are specific inhibitors of Human leukocyte elastase (HLE). Upon contact with HLE these compounds are cleaved to form a chromogenic or fluorogenic species which may be readily measured by the assay disclosed herein. The assay thus provides a means for direct measurement of the amount of active HLE in a body fluid or other sample.

  本发明涉及一种公式I的.beta.-内酰胺，其中X是具有色素或荧光基团的取代芳基或杂环芳基，是人类白细胞弹性蛋白酶（HLE）的特异性抑制剂。这些化合物在接触HLE时会被切割形成一种色素或荧光物种，可以通过此处披露的测定方法轻松测量。因此，该测定方法提供了一种直接测量体液或其他样品中活性HLE数量的手段。
• Labelled elastase inhibitors
  申请人：Amersham International PLC

  公开号：US06375926B1

  公开（公告）日：2002-04-23

  A human leucocyte elastase (HLE) inhibitor labelled with a detector moiety where the inhibitor is synthetic and has a molecular weight of less than 2000, is useful for the diagnostic imaging of sites of inflammation of infection in vivo, for labelling leucocytes in vitro, or for radiotherapy of rthritis. The HLE inhibitor is preferably a &bgr;-lactam or an azetidinone.

  人类白细胞弹性蛋白酶（HLE）抑制剂标记有检测物，其中抑制剂是合成的，分子量小于2000，可用于体内炎症或感染部位的诊断成像，体外标记白细胞，或治疗关节炎的放射治疗。 HLE抑制剂最好是β-内酰胺或氮杂环丙酮。