methyl 3-formyl-1-methyl-1H-indole-5-carboxylate

• 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: methyl 3-formyl-1-methyl-1H-indole-5-carboxylate
• 英文别名: Methyl 3-formyl-1-methylindole-5-carboxylate；methyl 3-formyl-1-methylindole-5-carboxylate
• 化学式: C₁₂H₁₁NO₃
• 分子量: 217.224
• InChiKey: NMKQVUSAPXYWFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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：

  3-(Thiadiazol-5-yl)-1,4-dihydropyrazol-5-one 、 methyl 3-formyl-1-methyl-1H-indole-5-carboxylate 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 1-methyl-3-(5-oxo-3-[1,2,3]thiadiazol-5-yl-1,5-dihydro-pyrazol-4-ylidenemethyl)-1H-indole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  1,2,3-Thiadiazole substituted pyrazolones as potent KDR/VEGFR-2 kinase inhibitors

  摘要：

  KDR kinase inhibition is considered to play an important role in regulating angiogenesis, which is vital for the survival and proliferation of tumor cells. Recently we disclosed a structure-based kinase inhibitor design strategy which led to the identification of a new class of VEGFR-2/KDR kinase inhibitors bearing heterocyclic substituted pyrazolones as the core template. Instability in a rat S9 preparation and poor iv PK profiles for most of these inhibitors necessitated exploration of new pyrazolones to identify new analogs with improved metabolic stability. Optimization of the heterocyclic moiety led to the identification of the thiadiazole series of pyrazolones (D) as potent VEGFR-2/KDR kinase inhibitors. SAR modifications, kinase selectivity profiling, and structural elements for improved PK properties were explored. Oral bioavailability up to 29% was achieved in the rat. Modeling results based on the Glide XP docking approach supported our postulation regarding the interaction of the lactam segment of the pyrazolones with the hinge region of the KDR kinase. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.054
• 作为产物：
  描述：

  1-甲基-1H-吲哚-5-羧酸甲酯 、 三甲胺 在 四丁基氟化铵 、 水 作用下， 反应 24.0h， 以60%的产率得到methyl 3-formyl-1-methyl-1H-indole-5-carboxylate
  参考文献：
  名称：

  可回收和可重复使用的n-Bu4NBF4 / PEG-400 / H2O系统，用于以Me3N作为羰基源的吲哚的电化学C-3甲酰化

  摘要：

  通过使用Me 3 N作为新型甲酰化试剂，开发了一种安全，实用且环保的电化学方法，用于合成3-甲酰化的吲哚。该方法避免了化学计量的氧化剂，金属催化剂和活化剂，并且将n -Bu 4 NBF 4 / PEG-400 / H 2 O的水相双相体系用作可循环和可重复使用的反应介质，从而实现了这种电合成方法更可持续和环保。该工艺扩大了N -EDG和N的底物范围和官能团耐受性-EWG吲哚。此外，通过这种途径实现了药物和天然产物的后期功能化和全部/正式合成。

  DOI：

  10.1039/d1gc00661d

文献信息

• 1,2,3-Thiadiazole substituted pyrazolones as potent KDR/VEGFR-2 kinase inhibitors
  作者：Rabindranath Tripathy、Arup Ghose、Jasbir Singh、Edward R. Bacon、Thelma S. Angeles、Shi X. Yang、Mark S. Albom、Lisa D. Aimone、Joseph L. Herman、John P. Mallamo

  DOI：10.1016/j.bmcl.2006.12.054

  日期：2007.3

  KDR kinase inhibition is considered to play an important role in regulating angiogenesis, which is vital for the survival and proliferation of tumor cells. Recently we disclosed a structure-based kinase inhibitor design strategy which led to the identification of a new class of VEGFR-2/KDR kinase inhibitors bearing heterocyclic substituted pyrazolones as the core template. Instability in a rat S9 preparation and poor iv PK profiles for most of these inhibitors necessitated exploration of new pyrazolones to identify new analogs with improved metabolic stability. Optimization of the heterocyclic moiety led to the identification of the thiadiazole series of pyrazolones (D) as potent VEGFR-2/KDR kinase inhibitors. SAR modifications, kinase selectivity profiling, and structural elements for improved PK properties were explored. Oral bioavailability up to 29% was achieved in the rat. Modeling results based on the Glide XP docking approach supported our postulation regarding the interaction of the lactam segment of the pyrazolones with the hinge region of the KDR kinase. (c) 2007 Elsevier Ltd. All rights reserved.
• Recyclable and reusable<i>n</i>-Bu₄NBF₄/PEG-400/H₂O system for electrochemical C-3 formylation of indoles with Me₃N as a carbonyl source
  作者：Fei Ling、Didi Cheng、Tao Liu、Lei Liu、Yujin Li、Jingyi Li、Weihui Zhong

  DOI：10.1039/d1gc00661d

  日期：——

  A safe, practical and eco-friendly electrochemical methodology for the synthesis of 3-formylated indoles has been developed by the utilization of Me3N as a novel formylating reagent. Stoichiometric oxidants, metal catalysts, and activating agents were avoided in this method, and an aqueous biphasic system of n-Bu4NBF4/PEG-400/H2O was used as a recyclable and reusable reaction medium, which made this

  通过使用Me 3 N作为新型甲酰化试剂，开发了一种安全，实用且环保的电化学方法，用于合成3-甲酰化的吲哚。该方法避免了化学计量的氧化剂，金属催化剂和活化剂，并且将n -Bu 4 NBF 4 / PEG-400 / H 2 O的水相双相体系用作可循环和可重复使用的反应介质，从而实现了这种电合成方法更可持续和环保。该工艺扩大了N -EDG和N的底物范围和官能团耐受性-EWG吲哚。此外，通过这种途径实现了药物和天然产物的后期功能化和全部/正式合成。