o-(methoxycarbonyl)-α-diazoacetophenone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: o-(methoxycarbonyl)-α-diazoacetophenone
• 英文别名: (1Z)-N-diazonio-2-methoxycarbonylbenzenecarboximidate
• 化学式: C₉H₇N₃O₃
• 分子量: 205.173
• InChiKey: VYGHSVNSICUOCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  o-(methoxycarbonyl)-α-diazoacetophenone 以 甲苯 为溶剂， 反应 2.0h， 生成 2-(甲氧基羰基)苯基异氰酸酯
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 4. Structure-Activity Relationships among N- and 3-Substituted 2,2'-Dithiobis(1H-indoles) for in vitro Inhibition of Receptor and Nonreceptor Protein Tyrosine Kinases

  摘要：

  A series of S-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC(50)s 1-20 mu M), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N-thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC(50)s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol-containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.

  DOI：

  10.1021/jm00001a011
• 作为产物：
  描述：

  2-(氯羰基)苯甲酸甲酯 在 sodium azide 作用下， 以 水 、 丙酮 为溶剂， 生成 o-(methoxycarbonyl)-α-diazoacetophenone
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 4. Structure-Activity Relationships among N- and 3-Substituted 2,2'-Dithiobis(1H-indoles) for in vitro Inhibition of Receptor and Nonreceptor Protein Tyrosine Kinases

  摘要：

  A series of S-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC(50)s 1-20 mu M), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N-thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC(50)s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol-containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.

  DOI：

  10.1021/jm00001a011

文献信息

• Chiral Lewis Acid-Catalyzed Enantioselective Cycloadditions between Indoles and Cyclic Carbonyl Ylides Derived from Diazodiketone or Diazoketoester Derivatives
  作者：Hiroyuki Suga、Yurie Sekikawa、Shunta Misawa、Daito Kinugawa、Rinnosuke Oda、Kennosuke Itoh、Yasunori Toda、Ryotaro Kiyono

  DOI：10.1021/acs.joc.5b00835

  日期：2015.7.2

  Asymmetric 1,3-dipolar cycloaddition reactions between N-methylindoles and several cyclic carbonyl ylides that were derived from diazodiketone or diazoketoester precursors in the presence of both achiral Rh and chiral lanthanoid metal catalysts are described. For the six-membered cyclic carbonyl ylides derived from 1-diazo-5-aryl-2,5-pentanedione precursors, the cycloaddition reactions were carried out using Rh-2(OAc)(4) (2 mol %) and the chiral Pybox-Ph-2 -Lu(OTf)(3) complex (10 mol %) as catalysts, resulting in high enantioselectivities (83% to >98% ee (exo)) along with relatively good exo-selectivities (exo:endo = 65:35 to 94:6) and yields (63-85%). For the five-membered cyclic carbonyl ylide derived from bromo-1-methylindole was carried out in the presence of Rh-2(OAc)(4) (2 mol%) and chiral Pybox-Ph-2-Er(OTf)(3) complex (30 mol %) as catalysts, resulting in relatively good enantioselectivity (78% ee) and endo-selectivity (endo:exo = 81:19).
• A practical solid phase synthesis of quinazoline-2,4-diones
  作者：Hui Shao、Marcus Colucci、Shaojing Tong、Hesheng Zhang、Arlindo L. Castelhano

  DOI：10.1016/s0040-4039(98)01595-0

  日期：1998.10

  We describe a practical solid phase synthesis of quinazoline-2,4-diones using a short-chain, high loading capacity, polyethyleneglycol polystyrene copolymer ("PEG(4)-PS" resin). The highlights of this synthesis include efficient acyl azide formation on the solid phase, Curtius rearrangement, and cyclocleavage with K2CO3 followed by simple product isolation. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Tyrosine Kinase Inhibitors. 4. Structure-Activity Relationships among N- and 3-Substituted 2,2'-Dithiobis(1H-indoles) for in vitro Inhibition of Receptor and Nonreceptor Protein Tyrosine Kinases
  作者：Brian D. Palmer、Gordon W. Rewcastle、Andrew M. Thompson、Maruta Boyd、H. D. Hollis Showalter、Anthony D. Sercel、David W. Fry、Alan J. Kraker、William A. Denny

  DOI：10.1021/jm00001a011

  日期：1995.1

  A series of S-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC(50)s 1-20 mu M), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N-thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC(50)s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol-containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.