dimethyl 6-benzyloxyquinoline-2,4-dicarboxylate | 438590-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: dimethyl 6-benzyloxyquinoline-2,4-dicarboxylate
• 英文别名: Dimethyl 6-phenylmethoxyquinoline-2,4-dicarboxylate
• CAS: 438590-22-8
• 化学式: C₂₀H₁₇NO₅
• 分子量: 351.359
• InChiKey: BHQGQFCHSCRWLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  74.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 6-benzyloxyquinoline-2,4-dicarboxylate 在 水 作用下， 以 四氢呋喃 为溶剂， 生成 6-(Benzyloxy)quinoline-2,4-dicarboxylic acid
  参考文献：
  名称：

  Quinoline-2,4-dicarboxylic acids: Synthesis and evaluation as inhibitors of the glutamate vesicular transport system

  摘要：

  Twenty-six quinoline-2,4-dicarboxylic acids (QDC's) were synthesized by a modified Doebner-von Miller pathway and tested as inhibitors against the glutamate vesicular transport (GVT) protein. The QDC's were active as inhibitors with the most potent QDC's found to contain halogens at the 6-/8-position, a hydroxyl at the 8-position, or a tethered aromatic moiety at the 6- or 7-position of the quinoline. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00444-8
• 作为产物：
  描述：

  alpha-酮戊二酸 在 氯化亚砜 、 2-甲基苯磺酸 、 溴 作用下， 以 二氯甲烷 为溶剂， 反应 27.5h， 生成 dimethyl 6-benzyloxyquinoline-2,4-dicarboxylate
  参考文献：
  名称：

  Synthesis and in Vitro Pharmacology of Substituted Quinoline-2,4-dicarboxylic Acids as Inhibitors of Vesicular Glutamate Transport

  摘要：

  The vesicular glutamate transport (VGLUT) system selectively mediates the uptake of L-glutamate into synaptic vesicles. Uptake is linked to an H+-ATPase that provides coupling among ATP hydrolysis, an electrochemical proton gradient, and glutamate transport. Substituted quinoline-2,4-dicarboxylic acids (QDCs), prepared by condensation of dimethyl keto-glutaconate (DKG) with substituted anilines and subsequent hydrolysis, were investigated as potential VGLUT inhibitors in synaptic vesicles. A brief panel of substituted QDCs was previously reported (Carrigan et al. Bioorg. Med. Chem. Lett. 1999, 9, 2607-2612), and showed that certain substituents led to more potent competitive inhibitors of VGLUT. Using these compounds as leads, an expanded series of QDC analogues were prepared either by condensation of DKG with novel anilines or via aryl-coupling (Suzuki or Heck) to dimethyl 6-bromoquino-linedicarboxylate. From the panel of almost 50 substituted QDCs tested as inhibitors of the VGLUT system, the 6-PhCH=CH-QDC (K-i = 167 muM), 6-PhCH2CH2-QDC (K-i = 143 muM), 6-(4'-phenylstyryl)-QDC (K-i = 64 AM), and 6-biphenyl-4-yl-QDC (K-i = 41 muM) were found to be the most potent blockers. A preliminary assessment of the key elements needed for binding to the VGLUT protein based on the structure-activity relationships for the panel of substituted QDCs is discussed herein. The substituted QDCs represent the first synthetically derived VGLUT inhibitors and are promising templates for the development of selective transporter inhibitors.

  DOI：

  10.1021/jm010261z

文献信息

• Quinoline-2,4-dicarboxylic acids: Synthesis and evaluation as inhibitors of the glutamate vesicular transport system
  作者：Christina N. Carrigan、C. Sean Esslinger、Richard D. Bartlett、Richard J. Bridges、Charles M. Thompson

  DOI：10.1016/s0960-894x(99)00444-8

  日期：1999.9

  Twenty-six quinoline-2,4-dicarboxylic acids (QDC's) were synthesized by a modified Doebner-von Miller pathway and tested as inhibitors against the glutamate vesicular transport (GVT) protein. The QDC's were active as inhibitors with the most potent QDC's found to contain halogens at the 6-/8-position, a hydroxyl at the 8-position, or a tethered aromatic moiety at the 6- or 7-position of the quinoline. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Synthesis and in Vitro Pharmacology of Substituted Quinoline-2,4-dicarboxylic Acids as Inhibitors of Vesicular Glutamate Transport
  作者：Christina N. Carrigan、Richard D. Bartlett、C. Sean Esslinger、Kimberly A. Cybulski、Pakamas Tongcharoensirikul、Richard J. Bridges、Charles M. Thompson

  DOI：10.1021/jm010261z

  日期：2002.5.1

  The vesicular glutamate transport (VGLUT) system selectively mediates the uptake of L-glutamate into synaptic vesicles. Uptake is linked to an H+-ATPase that provides coupling among ATP hydrolysis, an electrochemical proton gradient, and glutamate transport. Substituted quinoline-2,4-dicarboxylic acids (QDCs), prepared by condensation of dimethyl keto-glutaconate (DKG) with substituted anilines and subsequent hydrolysis, were investigated as potential VGLUT inhibitors in synaptic vesicles. A brief panel of substituted QDCs was previously reported (Carrigan et al. Bioorg. Med. Chem. Lett. 1999, 9, 2607-2612), and showed that certain substituents led to more potent competitive inhibitors of VGLUT. Using these compounds as leads, an expanded series of QDC analogues were prepared either by condensation of DKG with novel anilines or via aryl-coupling (Suzuki or Heck) to dimethyl 6-bromoquino-linedicarboxylate. From the panel of almost 50 substituted QDCs tested as inhibitors of the VGLUT system, the 6-PhCH=CH-QDC (K-i = 167 muM), 6-PhCH2CH2-QDC (K-i = 143 muM), 6-(4'-phenylstyryl)-QDC (K-i = 64 AM), and 6-biphenyl-4-yl-QDC (K-i = 41 muM) were found to be the most potent blockers. A preliminary assessment of the key elements needed for binding to the VGLUT protein based on the structure-activity relationships for the panel of substituted QDCs is discussed herein. The substituted QDCs represent the first synthetically derived VGLUT inhibitors and are promising templates for the development of selective transporter inhibitors.