6-Iodo-quinoline-2,4-dicarboxylic acid | 250641-15-7

• 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: 6-Iodo-quinoline-2,4-dicarboxylic acid
• 英文别名: 6-Iodo-2,4-quinolinedicarboxylic acid；6-iodoquinoline-2,4-dicarboxylic acid
• CAS: 250641-15-7
• 化学式: C₁₁H₆INO₄
• 分子量: 343.077
• InChiKey: YUIXTMDZGFKCOM-UHFFFAOYSA-N

物化性质

• 熔点：
  146-147 °C
• 沸点：
  518.6±50.0 °C(Predicted)
• 密度：
  2.093±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-Iodo-quinoline-2,4-dicarboxylic acid 在 palladium diacetate 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  NOVEL HIGH AFFINITY QUINOLINE-BASED KINASE LIGANDS

  摘要：

  公开号：

  EP1931657B1
• 作为产物：
  描述：

  alpha-酮戊二酸 在 氯化亚砜 、 2-甲基苯磺酸 、 hydroxide 、 溴 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.5h， 生成 6-Iodo-quinoline-2,4-dicarboxylic acid
  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

• Novel high affinity quinoline-based kinase ligands
  申请人：Deng Yongqi

  公开号：US20080045568A1

  公开（公告）日：2008-02-21

  Quinoline-based inhibitors of cyclin dependent kinase 2, compositions including the inhibitors, and methods of using the inhibitors and inhibitor compositions are described. The inhibitors and compositions including them are useful for treating disease or disease symptoms. The invention also provides for methods of making CDK-2 inhibitor compounds, methods of inhibiting CDK-2, and methods for treating disease or disease symptoms.

  基于喹啉的细胞周期蛋白依赖激酶2抑制剂，包括这些抑制剂的组合物，以及使用这些抑制剂和抑制剂组合物的方法。这些抑制剂和包括它们的组合物对治疗疾病或疾病症状有用。该发明还提供了制备CDK-2抑制剂化合物的方法，抑制CDK-2的方法，以及治疗疾病或疾病症状的方法。
• 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.
• US7511063B2
  申请人：——

  公开号：US7511063B2

  公开（公告）日：2009-03-31
• NOVEL HIGH AFFINITY QUINOLINE-BASED KINASE LIGANDS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1931657B1

  公开（公告）日：2013-12-25
• 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.