2-(5-Methyl-3-nitro-pyridin-2-yl)-malonic acid diethyl ester | 533910-47-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-(5-Methyl-3-nitro-pyridin-2-yl)-malonic acid diethyl ester
• 英文别名: diethyl 2-(5-methyl-3-nitropyridin-2-yl)propanedioate
• CAS: 533910-47-3
• 化学式: C₁₃H₁₆N₂O₆
• 分子量: 296.28
• InChiKey: AEPARRPAHKKTID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(5-Methyl-3-nitro-pyridin-2-yl)-malonic acid diethyl ester 在 铁粉 、 potassium carbonate 、 溶剂黄146 、 1-丙基磷酸酐 、 三乙胺 、 lithium chloride 、 lithium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.08h， 生成 N-(2-hydroxyethyl)-1-((6-methoxy-5-methylpyrimidin-4-yl)-methyl)-6-methyl-1H-pyrrolo[3,2-b]pyridine-3-carboxamide
  参考文献：
  名称：

  Azaindoles: Noncovalent DprE1 Inhibitors from Scaffold Morphing Efforts, Kill Mycobacterium tuberculosis and Are Efficacious in Vivo

  摘要：

  We report 1,4-azaindoles as a new inhibitor class that kills Mycobacterium tuberculosis in vitro and demonstrates efficacy in mouse tuberculosis models. The series emerged from scaffold morphing efforts and was demonstrated to noncovalently inhibit decaprenylphosphoryl-beta-D-ribose2'-epimerase (DprE1). With "drug-like" properties and no expectation of pre-existing resistance in the clinic, this chemical class has the potential to be developed as a therapy for drug-sensitive and drug-resistant tuberculosis.

  DOI：

  10.1021/jm401382v
• 作为产物：
  描述：

  2-氯-5-甲基-3-硝基吡啶 、 丙二酸二乙酯 在 sodium hydride 作用下， 以 乙二醇二甲醚 为溶剂， 反应 19.0h， 生成 2-(5-Methyl-3-nitro-pyridin-2-yl)-malonic acid diethyl ester
  参考文献：
  名称：

  1H-pyrrolo [3,2-b] pyridine-3-carboxylic acid amines as GABAA receptor ligands

  摘要：

  揭示了结合到GABAA受体的苯二氮卓酮位点的1H-吡咯[3,2-b]吡啶-3-羧酸酰胺。这类化合物可用于调节GABAA受体在体内和体外的配体结合，并在人类、家养伴侣动物和家畜动物的多种中枢神经系统（CNS）疾病治疗中特别有用。

  公开号：

  US06673811B1

文献信息

• Lead Optimization of 1,4-Azaindoles as Antimycobacterial Agents
  作者：Pravin S. Shirude、Radha K. Shandil、M. R. Manjunatha、Claire Sadler、Manoranjan Panda、Vijender Panduga、Jitendar Reddy、Ramanatha Saralaya、Robert Nanduri、Anisha Ambady、Sudha Ravishankar、Vasan K. Sambandamurthy、Vaishali Humnabadkar、Lalit K. Jena、Rudrapatna S. Suresh、Abhishek Srivastava、K. R. Prabhakar、James Whiteaker、Robert E. McLaughlin、Sreevalli Sharma、Christopher B. Cooper、Khisi Mdluli、Scott Butler、Pravin S. Iyer、Shridhar Narayanan、Monalisa Chatterji

  DOI：10.1021/jm500571f

  日期：2014.7.10

  In a previous report, we described the discovery of 1,4-azaindoles, a chemical series with excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-beta-D-ribose-2'-epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. Herein, we report lead optimization of this series, culminating in potent, metabolically stable compounds that have a robust pharmacokinetic profile without any PDE6 liability. Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB infection model. We believe that compounds from the 1,4-azaindole series are suitable for in vivo combination and safety studies.
• Journal of Medicinal Chemistry 2014, 57, 5728-5737
  作者：

  DOI：——

  日期：——
• 1H-PYRROLO(3,2-B)PYRIDINE-3-CARBOXYLIC ACID AMIDES
  申请人：Neurogen Corporation

  公开号：EP1453831A1

  公开（公告）日：2004-09-08
• US6673811B1
  申请人：——

  公开号：US6673811B1

  公开（公告）日：2004-01-06
• [EN] 1H-PYRROLO[3,2-B]PYRIDINE-3-CARBOXYLIC ACID AMIDES<br/>[FR] AMIDES D'ACIDE 1H-PYRROLO[3,2-B]PYRIDINE-3-CARBOXYLIQUE
  申请人：NEUROGEN CORP

  公开号：WO2003044018A1

  公开（公告）日：2003-05-30

  Disclosed are 1H-Pyrrolo[3,2-b]pyridine-3-carboxylic acid amides that bind to the benzodiazepine site of GABAA receptors. Such compounds can be used to modulate ligand binding to GABAA receptors in vivo and in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals, and livestock animals.