Cyclohexylmethyl-diazomethylketon | 27473-43-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: Cyclohexylmethyl-diazomethylketon
• 英文别名: (3E)-1-cyclohexyl-3-diazopropan-2-one
• CAS: 27473-43-4
• 化学式: C₉H₁₄N₂O
• 分子量: 166.223
• InChiKey: XSQMRVVOOYLFIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  19.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Cyclohexylmethyl-diazomethylketon 在 三氟化硼乙醚 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 16.75h， 生成 N-[5-(5-Cyclohexylmethyl-oxazol-2-ylmethylsulfanyl)-thiazol-2-yl]-acetamide
  参考文献：
  名称：

  Discovery of Aminothiazole Inhibitors of Cyclin-Dependent Kinase 2:  Synthesis, X-ray Crystallographic Analysis, and Biological Activities

  摘要：

  High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC50 values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2.

  DOI：

  10.1021/jm0201520
• 作为产物：
  描述：

  环己基乙酸 在 氯化亚砜 、 二乙二醇乙醚 、 N,N-二甲基甲酰胺 、 potassium hydroxide 作用下， 以 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 Cyclohexylmethyl-diazomethylketon
  参考文献：
  名称：

  通过化学酶组装和环丙基酮多样化的手性环丙烷支架的多样化库

  摘要：

  手性环丙烷环是药物和生物活性天然产物中的关键药效​​团，使这些构件库成为药物发现和开发活动的宝贵资源。在这里，我们报告了用于立体选择性组装和环丙基酮结构多样化的化学酶策略的开发，这是一种高度通用但尚未开发的功能化环丙烷类。抹香鲸肌红蛋白的工程变体显示出能够在重氮酮卡宾供体试剂存在下通过烯烃环丙烷化高度非对映和对映选择性构建这些分子。这种生物催化剂提供了非常广泛的底物范围，在各种乙烯基芳烃底物以及一系列不同的α-芳基和α-烷基重氮酮衍生物中以高立体选择性催化该反应。这些酶产物的化学转化使这些分子能够进一步多样化，以产生一系列结构多样的含环丙烷的对映体形式的支架，包括在药物和天然产物中发现的核心基序以及新结构。这项工作说明了将生物生物催化与化学酶合成相结合以产生对药物化学和药物发现具有高价值的光学活性支架集合的力量。这些酶产物的化学转化使这些分子能够进一步多样化，以产生一系列结构多样的含环丙烷

  DOI：

  10.1021/jacs.0c09504

文献信息

• Studies on hypolipidemic agents. III. Synthesis and esterase-inhibitory activity of .OMEGA.-cycloalkyl-2-oxoalkyl arenesulfonates.
  作者：KAZUO OGAWA、TADAFUMI TERADA、YOSHIYUKI MURANAKA、TOSHIHIRO HAMAKAWA、SETSURO FUJII

  DOI：10.1248/cpb.35.2426

  日期：——

  Various ω-cycloalkyl-2-oxoalkyl arenesulfonates were synthesized and evaluated for esterase-and chymotrypsin-inhibitory activities and hypolipidemic activity. Among the tested compounds, 2-oxoalkyl arenesulfonates (4, 8 and 13) having a cyclohexyl substituent at the terminus of the alkyl chain exhibited considerable esterase-inhibitory activity, and several compounds among 4 and 8 also exhibited potent hypolipidemic action. The structure-activity relationships of these compounds are discussed.

  多种ω-环烷基-2-氧代烷基芳磺酸酯被合成，并评估了其酯酶和胰凝乳蛋白酶抑制活性以及降血脂活性。在测试的化合物中，具有烷基链末端环己基取代的2-氧代烷基芳磺酸酯（4、8和13）表现出显著的酯酶抑制活性，而4和8中的几种化合物还显示出强大的降血脂作用。本文讨论了这些化合物的结构-活性关系。
• .alpha.-Halo-2-oxo-1-azetidinemethane-carboxylic acid compounds
  申请人：Ciba-Geigy Corporation

  公开号：US04161476A1

  公开（公告）日：1979-07-17

  .alpha.-Hydroxy-2-oxo-1-azetidinemethane-carboxylic acid compounds of formula ##STR1## wherein R.sub.1 represents a hydrogen atom or the organic residue of an alcohol, R.sub.2 represents a hydrogen atom or an acyl residue, R.sub.3 represents an organic residue and R.sub.4 represents a hydrogen atom, when R.sub.2 stands for an acyl residue, or the two groups R.sub.3 and R.sub.4 together represent a disubstituted carbon atom, when R.sub.2 stands for a hydrogen atom or an acyl group, are useful as intermediates for the manufacture of pharmacologically active compounds.

  .alpha.-羟基-2-氧代-1-氮杂环甲烷羧酸化合物，其化学式为##STR1##其中R.sub.1代表氢原子或醇的有机残基，R.sub.2代表氢原子或酰基残基，R.sub.3代表有机残基，R.sub.4代表氢原子（当R.sub.2代表酰基残基时），或R.sub.3和R.sub.4两个基团一起代表一个二取代的碳原子（当R.sub.2代表氢原子或酰基时），这些化合物用作制造药理活性化合物的中间体。
• Oxyacetic acid compounds and process for their manufacture
  申请人：Ciba-Geigy Corporation

  公开号：US04052408A1

  公开（公告）日：1977-10-04

  .alpha.-Hydroxy-2-oxo-1-azetidinemethane-carboxylic acid compounds of formula ##STR1## wherein R.sub.1 represents a hydrogen atom or the organic residue of an alcohol, R.sub.2 represents a hydrogen atom or an acyl residue, R.sub.3 represents an organic residue and R.sub.4 represents a hydrogen atom, when R.sub.2 stands for an acyl residue, or the two groups R.sub.3 and R.sub.4 together represent a disubstituted carbon atom, when R.sub.2 stands for a hydrogen atom or an acyl group, are useful as intermediates for the manufacture of pharmacologically active compounds.

  .alpha.-羟基-2-氧代-1-氮杂丁甲酸化合物的化学式为##STR1## 其中R.sub.1代表氢原子或醇的有机残基，R.sub.2代表氢原子或酰基残基，R.sub.3代表有机残基，R.sub.4代表氢原子（当R.sub.2代表酰基残基时），或R.sub.3和R.sub.4两个基团共同代表一个二取代碳原子（当R.sub.2代表氢原子或酰基时），作为制造药理活性化合物的中间体具有用处。
• Cyclopentanone synthesis by intramolecular carbon-hydrogen insertion of diazo ketones. A diterpene-to-steroid skeleton conversion
  作者：Ernest Wenkert、Linda L. Davis、Banavara L. Mylari、Mary F. Solomon、Roberto R. Da Silva、Sol Shulman、Ronald J. Warnet、Paolo Ceccherelli、Massimo Curini、Roberto Pellicciari

  DOI：10.1021/jo00138a008

  日期：1982.8
• Altering the Communication Networks of Multispecies Microbial Systems Using a Diverse Toolbox of AI-2 Analogues
  作者：Sonja Gamby、Varnika Roy、Min Guo、Jacqueline A. I. Smith、Jingxin Wang、Jessica E. Stewart、Xiao Wang、William E. Bentley、Herman O. Sintim

  DOI：10.1021/cb200524y

  日期：2012.6.15

  There have been intensive efforts to find small molecule antagonists for bacterial quorum sensing (QS) mediated by the "universal" QS autoinducer, AI-2. Previous work has shown that linear and branched aryl analogues of AI-2 can selectively modulate AI-2 signaling in bacteria. Additionally, LsrK-dependent phosphorylated analogues have been implicated as the active inhibitory form against AI-2 signaling. We used these observations to synthesize an expanded and diverse array of AI-2 analogues, which included aromatic as well as cyclic C-1-alkyl analogues. Species-specific analogues that disrupted AI-2 signaling in Escherichia coli and Salmonella typhimurium were identified. Similarly, analogues that disrupted QS behaviors in Pseudomonas aeruginosa were found. Moreover, we observed a strong correlation between LsrK-dependent phosphorylation of these acyl analogues and their ability to suppress QS. Significantly, we demonstrate that these analogues can selectively antagonize QS in single bacterial strains in a physiologically relevant polymicrobial culture.