6-氯喹啉-2,4-二羧酸 | 62482-28-4

• 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
• 中文名称: 6-氯喹啉-2,4-二羧酸
• 英文名称: 6-chloroquinoline-2,4-dicarboxylic acid
• 英文别名: 6-chloroquinolin-2,4-dicarboxylic acid；6-chloro-quinoline-2,4-dicarboxylic acid；6-Chlor-chinolin-2,4-dicarbonsaeure
• CAS: 62482-28-4
• 化学式: C₁₁H₆ClNO₄
• 分子量: 251.626
• InChiKey: ILQAFAWQKBSEDK-UHFFFAOYSA-N

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

安全信息

• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  描述：

  6-氯喹啉-2,4-二羧酸 在 氯化亚砜 、 二苯醚 、 联苯 作用下， 生成 6-chloro-quinoline-4-carbonyl chloride ; hydrochloride
  参考文献：
  名称：

  抗疟药；6和7-氯-α-（二烷基氨基甲基）-4-喹啉二甲醇。

  摘要：

  DOI：

  10.1021/ja01198a010
• 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-氯喹啉-2,4-二羧酸
  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

• [EN] NOVEL FAP INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE FAP
  申请人：UNIV ANTWERPEN

  公开号：WO2013107820A1

  公开（公告）日：2013-07-25

  The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.

  本发明涉及对FAP（成纤维细胞活化蛋白）具有高选择性和特异性的新型抑制剂。所述抑制剂可用作人类和/或兽药，特别是用于治疗和/或预防FAP相关疾病，如但不限于增殖性疾病。
• NOVEL FAP INHIBITORS
  申请人：UNIVERSITEIT ANTWERPEN

  公开号：US20140357650A1

  公开（公告）日：2014-12-04

  The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.

  本发明涉及具有高选择性和特异性的新型抑制剂，用于FAP（成纤维细胞激活蛋白）。所述抑制剂可用作人类和/或兽医药物，特别用于治疗和/或预防与FAP相关的疾病，如但不限于增殖性疾病。
• [EN] GLUCOSE TRANSPORT INHIBITORS<br/>[FR] INHIBITEURS DE TRANSPORT DU GLUCOSE
  申请人：BAYER PHARMA AG

  公开号：WO2015091428A1

  公开（公告）日：2015-06-25

  The present invention relates to chemical compounds that selectively inhibit glucose transporter 1 (GLUT1), to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, as well as to intermediate compounds useful in the preparation of said compounds.

  本发明涉及选择性抑制葡萄糖转运蛋白1（GLUT1）的化合物，涉及制备该类化合物的方法，包括含有该类化合物的药物组合物和药物组合物，以及利用该类化合物制造用于治疗或预防疾病的药物组合物的用途，还涉及在制备该类化合物中有用的中间体化合物。
• Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold
  作者：Koen Jansen、Leen Heirbaut、Jonathan D. Cheng、Jurgen Joossens、Oxana Ryabtsova、Paul Cos、Louis Maes、Anne-Marie Lambeir、Ingrid De Meester、Koen Augustyns、Pieter Van der Veken

  DOI：10.1021/ml300410d

  日期：2013.5.9

  Fibroblast activation protein (FAP) is a serine protease that is generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) and prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have explored the effects of substituting the quinoline ring and varying the position of its sp(2) hybridized nitrogen atom. The most promising inhibitors combined low nanomolar FAP inhibition and high selectivity indices (>10(3)) with respect to both the DPPs and PREP. Preliminary experiments on a representative inhibitor demonstrate that plasma stability, kinetic solubility, and log D of this class of compounds can be expected to be satisfactory.
• 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.