4-氯-6,8-二氟喹啉-3-甲酸乙酯 | 150258-20-1

• 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: 4-氯-6,8-二氟喹啉-3-甲酸乙酯
• 英文名称: 4-chloro-6,8-difluoro-3-ethoxycarbonylquinoline
• 英文别名: ethyl 4-chloro-6,8-difluoroquinoline-3-carboxylate
• CAS: 150258-20-1
• 化学式: C₁₂H₈ClF₂NO₂
• mdl: MFCD00173353
• 分子量: 271.651
• InChiKey: HLIWQEZYRYNMMV-UHFFFAOYSA-N

物化性质

• 沸点：
  329.9±37.0 °C(Predicted)
• 密度：
  1.418±0.06 g/cm3(Predicted)
• 稳定性/保质期：
  避氧化物

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-氯-6,8-二氟喹啉-3-甲酸乙酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 以60%的产率得到6,8-Difluoro-2,5-dihydro-pyrazolo[4,3-c]quinolin-3-one
  参考文献：
  名称：

  Savini; Massarelli; Corti, Il Farmaco, 1993, vol. 48, # 12, p. 1675 - 1686

  摘要：

  DOI：
• 作为产物：
  描述：

  ethyl 6,8-difluoro-4-hydroxyquinoline-3-carboxylate 在 三氯氧磷 作用下， 生成 4-氯-6,8-二氟喹啉-3-甲酸乙酯
  参考文献：
  名称：

  Savini; Massarelli; Corti, Il Farmaco, 1993, vol. 48, # 12, p. 1675 - 1686

  摘要：

  DOI：

文献信息

• High affinity central benzodiazepine receptor ligands: synthesis and structure–activity relationship studies of a new series of pyrazolo[4,3- c ]quinolin-3-ones
  作者：L. Savini、P. Massarelli、C. Nencini、C. Pellerano、G. Biggio、A. Maciocco、G. Tuligi、A. Carrieri、N. Cinone、A. Carotti

  DOI：10.1016/s0968-0896(97)10039-6

  日期：1998.4

  tested as central benzodiazepine receptor ligands. Results from structure-affinity relationship studies were in full agreement with previously proposed pharmacophore models and, in addition, quantitative structure-activity analysis gave further significant insight into the main molecular determinants of high benzodiazepine receptor affinity. The intrinsic activity of some active ligands was also determined

  制备了一系列在喹啉和N2-苯环上带有适当取代基的2-芳基（杂芳基）-2,5-二氢吡唑并[4,3-c]喹啉-3-（3H）-酮，并进行了测试。中央苯并二氮杂receptor受体配体。结构亲和关系研究的结果与先前提出的药效团模型完全吻合，此外，定量结构活性分析为高苯并二氮杂receptor受体亲和力的主要分子决定因素提供了更重要的见解。还确定并初步讨论了一些活性配体的内在活性。
• Metabotropic glutamate receptor antagonists and their use for treating central nervous system diseases
  申请人：NPS Pharmaceuticals, Inc.

  公开号：US06429207B1

  公开（公告）日：2002-08-06

  The present invention provides compounds, and pharmaceutical compositions containing those compounds, that are active at metabotropic glutamate receptors. The compounds are useful for treating neurological diseases and disorders. Methods of preparing the compounds also are disclosed.

  本发明提供了在代谢型谷氨酸受体上具有活性的化合物和含有这些化合物的药物组合物，这些化合物对治疗神经系统疾病和障碍是有用的。同时还公开了制备这些化合物的方法。
• Quinoline compounds
  申请人：Sugen, Inc.

  公开号：US05650415A1

  公开（公告）日：1997-07-22

  A method of inhibiting cell proliferation or differentiation by exposing a cell to a compound of the formula ##STR1## or a pharmaceutically acceptable salt thereof. Q is selected from the group consisting of NH and S, n is 0 or 1; and R.sub.1-9 are independently selected from the group consisting of halo, trihalomethyl, alkyl, nitro, hydroxy, alkoxy, sulphoxy, sulphonyl, amide, sulfonamide, carboxamide, amino, and hydrogen. Also provided is a compound of the structure ##STR2##

  一种通过将细胞暴露于公式##STR1##的化合物或其药学上可接受的盐中，抑制细胞增殖或分化的方法。其中，Q从NH和S组成的群体中选择，n为0或1；R.sub.1-9分别从卤、三卤甲基、烷基、硝基、羟基、烷氧基、硫氧基、磺酰基、酰胺、磺酰胺、羧酰胺、氨基和氢中独立选择。还提供了结构式##STR2##的化合物。
• Discovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity
  作者：Shyh-Ming Yang、Natalia J. Martinez、Adam Yasgar、Carina Danchik、Catrine Johansson、Yuhong Wang、Bolormaa Baljinnyam、Amy Q. Wang、Xin Xu、Pranav Shah、Dorian Cheff、Xinran S. Wang、Jacob Roth、Madhu Lal-Nag、James E. Dunford、Udo Oppermann、Vasilis Vasiliou、Anton Simeonov、Ajit Jadhav、David J. Maloney

  DOI：10.1021/acs.jmedchem.8b00270

  日期：2018.6.14

  Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) and possess vital physiological and toxicological functions in areas such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of certain ALDHs (e.g., ALDHIAI) is an important biomarker in cancers and cancer stem cells (CSCs) indicating the potential need for the identification and development of small molecule ALDH inhibitors. Herein, a newly designed series of quinoline-based analogs of ALDH1A1 inhibitors is described. Extensive medicinal chemistry optimization and biological characterization led to the identification of analogs with significantly improved enzymatic and cellular ALDH inhibition. Selected analogs, e.g., 86 (NCT-505) and 91 (NCT-506), demonstrated target engagement in a cellular thermal shift assay (CETSA), inhibited the formation of 3D spheroid cultures of OV-90 cancer cells, and potentiated the cytotoxicity of paclitaxel in SKOV-3-TR, a paclitaxel resistant ovarian cancer cell line. Lead compounds also exhibit high specificity over other ALDH isozymes and unrelated dehydrogenases. The in vitro ADME profiles and pharmacokinetic evaluation of selected analogs are also highlighted.
• High affinity central benzodiazepine receptor ligands. Part 2: quantitative structure–activity relationships and comparative molecular field analysis of pyrazolo[4,3- c ]quinolin-3-ones
  作者：L. Savini、L. Chiasserini、C. Pellerano、G. Biggio、E. Maciocco、M. Serra、N. Cinone、A. Carrieri、C. Altomare、A. Carotti

  DOI：10.1016/s0968-0896(00)00262-5

  日期：2001.2

  A large series of 2-aryl(heteroaryl)-2,5-dihydropyrazolo[4,3-c]quinolin-3(3H)-ones (PQ, 106 compounds), carrying appropriate substituents at the quinoline and N-2-phenyl rings, were designed, prepared and tested as central benzodiazepine receptor ligands. Compounds with an affinity significantly higher than the parent compound CGS-8216 were obtained, the most active ligand showing a pIC(50) = 10.35. Hansch and comparative molecular field analyses gave coherent results suggesting the main structural requirements of high receptor binding affinity. The possible formation of a three-centred hydrogen bond (HB) at the HB donor site H-2, as a key interaction for high receptor binding affinity, was assessed by the calculation and comparison of the molecular electrostatic potentials of a series of selected ligands. (C) 2001 Elsevier Science Ltd. All rights reserved.