ethyl 3-(1-methyl-1H-indol-2-yl)-3-oxopropanoate | 951784-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 3-(1-methyl-1H-indol-2-yl)-3-oxopropanoate
• 英文别名: ethyl 3-(1-methylindol-2-yl)-3-oxopropanoate
• CAS: 951784-99-9
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: DILUCQGHQGAHLT-UHFFFAOYSA-N

物化性质

• 沸点：
  383.9±17.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 3-(1-methyl-1H-indol-2-yl)-3-oxopropanoate 在 哌啶 、 nickel(II) bis[bis((trifluoromethyl)sulfonyl)amide] 、 (1E,1'E)-N,N'-((1S,2S)-cyclohexane-1,2-diyl)bis(1-(quinolin-2-yl)methanimine) 、 溶剂黄146 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 4.3h， 生成 ethyl (1S,2R)-4-methyl-3-oxo-1-phenyl-1,2,3,4-tetrahydrocyclopenta[b]indole-2-carboxylate 、 ethyl 4-methyl-3-oxo-1-phenyl-1,2,3,4-tetrahydrocyclopenta[b]indole-2-carboxylate
  参考文献：
  名称：

  Catalytic Asymmetric Nazarov Cyclization of Heteroaryl Vinyl Ketones through a Crystallographically Defined Chiral Dinuclear Nickel Complex

  摘要：

  A Ni(NTf2)(2) and tetradentate bisimino-bisquinoline ligand complex catalyzed the enantioselective Nazarov cyclization of heteroaryl vinyl ketones. An X-ray-quality crystal was obtained from a mixture of the Ni complex and the substrate, which was the dinuclear chiral Ni complex. From information regarding the structure of the complex, the substrate was distorted to form a helical shape, and the carbon atoms involved in bond formation were close to each other. In addition, mechanistic studies revealed that the configuration of the olefin moiety was isomerized before bond formation.

  DOI：

  10.1021/acs.orglett.5b02497
• 作为产物：
  描述：

  1-甲基吲哚-2-甲酸 在 草酰氯 、 N,N-二甲基甲酰胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 ethyl 3-(1-methyl-1H-indol-2-yl)-3-oxopropanoate
  参考文献：
  名称：

  Catalytic Asymmetric Nazarov Cyclization of Heteroaryl Vinyl Ketones through a Crystallographically Defined Chiral Dinuclear Nickel Complex

  摘要：

  A Ni(NTf2)(2) and tetradentate bisimino-bisquinoline ligand complex catalyzed the enantioselective Nazarov cyclization of heteroaryl vinyl ketones. An X-ray-quality crystal was obtained from a mixture of the Ni complex and the substrate, which was the dinuclear chiral Ni complex. From information regarding the structure of the complex, the substrate was distorted to form a helical shape, and the carbon atoms involved in bond formation were close to each other. In addition, mechanistic studies revealed that the configuration of the olefin moiety was isomerized before bond formation.

  DOI：

  10.1021/acs.orglett.5b02497

文献信息

• Cdc7 Kinase Inhibitors: 5-Heteroaryl-3-Carboxamido-2-Aryl Pyrroles as Potential Antitumor Agents. 1. Lead Finding
  作者：Maria Menichincheri、Clara Albanese、Cristina Alli、Dario Ballinari、Alberto Bargiotti、Marina Caldarelli、Antonella Ciavolella、Alessandra Cirla、Maristella Colombo、Francesco Colotta、Valter Croci、Roberto D’Alessio、Matteo D’Anello、Antonella Ermoli、Francesco Fiorentini、Barbara Forte、Arturo Galvani、Patrizia Giordano、Antonella Isacchi、Katia Martina、Antonio Molinari、Jürgen K. Moll、Alessia Montagnoli、Paolo Orsini、Fabrizio Orzi、Enrico Pesenti、Antonio Pillan、Fulvia Roletto、Alessandra Scolaro、Marco Tatò、Marcellino Tibolla、Barbara Valsasina、Mario Varasi、Paola Vianello、Daniele Volpi、Corrado Santocanale、Ermes Vanotti

  DOI：10.1021/jm100504d

  日期：2010.10.28

  we report on a new chemical class of 5-heteroaryl-3-carboxamido-2-substituted pyrroles (1A) that offers advantages of chemistry diversification and synthetic simplification. This work led to the identification of compound 18, with biochemical data and ADME profile similar to those of compound 1 but characterized by superior efficacy in an in vivo model. Derivative 18 represents a new lead compound worthy

  Cdc7丝氨酸/苏氨酸激酶是真核生物中DNA合成的关键调节剂。通过si RNA或原型小分子对Cdc7的抑制在肿瘤细胞中引起p53独立凋亡，同时可逆地阻止初级成纤维细胞的细胞周期进程。这暗示着Cdc7激酶可以被认为是抗癌治疗的潜在靶标。我们先前曾报道吡咯并吡啶并酮（例如1）是Cdc7激酶的有效和选择性抑制剂，具有良好的细胞效力和体外ADME特性，但药代动力学不理想。在这里我们报告了一种新的化学类别的5-杂芳基-3-羧酰胺基-2-取代的吡咯（1A）具有化学多样化和合成简化的优势。这项工作导致了化合物18的鉴定，其生化数据和ADME谱与化合物1相似，但在体内模型中具有优越的功效。衍生物18代表一种新的先导化合物，值得进一步研究，以最终确定出临床候选药物。