ethyl 4,5,7-trichloroquinoline-3-carboxylate | 150258-21-2

• 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: ethyl 4,5,7-trichloroquinoline-3-carboxylate
• CAS: 150258-21-2
• 化学式: C₁₂H₈Cl₃NO₂
• mdl: MFCD00173410
• 分子量: 304.56
• InChiKey: JUHHXTUPYVWFKJ-UHFFFAOYSA-N

物化性质

• 熔点：
  69-71 °C
• 沸点：
  389.3±37.0 °C(Predicted)
• 密度：
  1.471±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 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：
  3

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  ethyl 4,5,7-trichloroquinoline-3-carboxylate 在 一水合肼 作用下， 以 乙醇 为溶剂， 以60%的产率得到7,9-Dichloro-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：

  3,5-二氯苯胺 在 三氯氧磷 作用下， 以 二苯醚 、 乙醇 为溶剂， 反应 2.75h， 生成 ethyl 4,5,7-trichloroquinoline-3-carboxylate
  参考文献：
  名称：

  新型3-（喹啉-4-基氨基）苯磺酰胺作为碳酸酐酶同工型I和II抑制剂的合成及生物学评价

  摘要：

  抽象的 碳酸酐酶（CAs，EC 4.2.1.1）是涉及多种生物过程的关键金属酶。我们报告了合成和生物学评估的新系列的苯磺酰胺结合未/取代的乙基喹啉-3-羧酸酯部分。新合成的化合物在体外评估为胞质人（h）亚型hCA I和II的抑制剂。此处报道的喹啉在不同程度上均抑制了hCA I和II亚型：h CA I在0.966–9.091μM范围内被K I s抑制，而hCA II在0.083–3.594μM范围内被抑制。主7-氯-6- flouro取代sulphfonamide衍生物6E（ķ我 = 0.083μM）被证明是抑制hCA II活性最强的喹啉，而其次磺酰胺类似物未能抑制hCA II直至10μM，从而证实了主要的磺酰胺类作为锌结合基团的关键作用。 CA抑制活性。

  DOI：

  10.1080/14756366.2019.1652282

文献信息

• Synthesis and preliminary structure-activity relationship study of 2-aryl-2<i>H</i>-pyrazolo[4,3-<i>c</i>]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
  作者：Ivana Malvacio、Alberto Cuzzolin、Mattia Sturlese、D. Mariano A. Vera、E. Laura Moyano、Stefano Moro

  DOI：10.1080/14756366.2017.1404592

  日期：2018.1.1

  arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised

  丝氨酸-苏氨酸检查点激酶1（Chk1）在细胞周期停滞中起着至关重要的作用，以响应DNA损伤。在过去的十年中，Chk1抑制剂已成为增强细胞毒性化学治疗剂抗肿瘤功效的新型治疗策略。在寻找新的Chk1抑制剂时，首次通过体外和计算机模拟方法评估了同类的2-芳基-2 H-吡唑并[4,3-c]喹啉-3-酮（PQ）。 。使用常规或微波加热以良好至极好的产率合成了总共30个PQ结构，突出显示其中14个是新的化学实体。值得注意的是，在这项初步研究中，两种化合物4e2和4h2已显示Chk1激酶的基础活性适度但显着降低。从这些初步结果开始，
• An alternative approach toward 2-aryl-2H-pyrazolo[4,3-c]-quinolin-3-ones by a multistep synthesis
  作者：Marisa J. López Rivilli、Elizabeth L. Moyano、Gloria I. Yranzo

  DOI：10.1016/j.tetlet.2009.10.123

  日期：2010.1

  carried out starting from dichloro- and bromoanilines (1a–b) and diethyl 2-(ethoxymethylene)malonate using a slightly modified Gould-Jacobs reaction. In this work we present a novel chlorination strategy to prepare quinoline derivatives 4 in excellent yields as key intermediates in the synthesis of the target compounds. Several reaction conditions were evaluated to optimize the formation of pyrazoloquinolinone

  方便地制备了一系列2-芳基-2 H-吡唑并[4，3 - c ]喹啉-3-酮衍生物6和7。从二氯苯甲烷和溴苯胺（1a – b）到2-（乙氧基亚甲基）丙二酸二乙酯，使用经过稍微修饰的Gould-Jacobs反应进行了多步合成。在这项工作中，我们提出了一种新颖的氯化策略，以高收率制备喹啉衍生物4作为目标化合物合成中的关键中间体。评价了几种反应条件以优化吡唑并喹啉酮核的形成。两种氯喹啉酮4a–b的化学行为差异 还讨论了与芳基和苄基肼形成的芳基。
• Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamides as carbonic anhydrase isoforms I and II inhibitors
  作者：Mohammad M. Al-Sanea、Ahmed Elkamhawy、Sora Paik、Silvia Bua、So Ha Lee、Mohamed A. Abdelgawad、Eun Joo Roh、Wagdy M. Eldehna、Claudiu T. Supuran

  DOI：10.1080/14756366.2019.1652282

  日期：2019.1.1

  crucial metalloenzymes that are involved in diverse bioprocesses. We report the synthesis and biological evaluation of novel series of benzenesulfonamides incorporating un/substituted ethyl quinoline-3-carboxylate moieties. The newly synthesised compounds were in vitro evaluated as inhibitors of the cytosolic human (h) isoforms hCA I and II. Both isoforms hCA I and II were inhibited by the quinolines

  抽象的 碳酸酐酶（CAs，EC 4.2.1.1）是涉及多种生物过程的关键金属酶。我们报告了合成和生物学评估的新系列的苯磺酰胺结合未/取代的乙基喹啉-3-羧酸酯部分。新合成的化合物在体外评估为胞质人（h）亚型hCA I和II的抑制剂。此处报道的喹啉在不同程度上均抑制了hCA I和II亚型：h CA I在0.966–9.091μM范围内被K I s抑制，而hCA II在0.083–3.594μM范围内被抑制。主7-氯-6- flouro取代sulphfonamide衍生物6E（ķ我 = 0.083μM）被证明是抑制hCA II活性最强的喹啉，而其次磺酰胺类似物未能抑制hCA II直至10μM，从而证实了主要的磺酰胺类作为锌结合基团的关键作用。 CA抑制活性。
• Synthesis and pharmacological evaluation of pyrazolo[4,3-c]quinolinones as high affinity GABAA-R ligands and potential anxiolytics
  作者：Marisa J. López Rivilli、Anahí V. Turina、Elena A. Bignante、Victor H. Molina、María A. Perillo、Margarita C. Briñon、Elizabeth L. Moyano

  DOI：10.1016/j.bmc.2018.06.021

  日期：2018.8

  aryl-hydrazines affording the final compounds. PQs exhibited different potency in displacing specific [3H]Flunitrazepam binding from the benzodiazepine binding site at the γ-aminobutyric acid receptor (GABAA-R) depending on the substitution of the pyrazoloquinolone nucleus. PCA helped determine how different substituents contributed to the differential behavior of the PQs studied. Compounds with high affinity for

  报道了一系列吡唑并[4,3 - c ]喹啉-3-酮（PQs）的合成，体外配体结合研究和体内高架迷宫测试（EPM）。PQ的多步合成从苯胺和2-（乙氧基亚甲基）丙二酸二乙酯开始，通过Gould-Jacobs反应生成quinolin-4-one核。将这些喹啉酮转化为4-氯喹啉，使其与芳基肼反应，得到最终化合物。PQS在移位特定[表现出各种不同效价3 H]氟硝西泮从苯并二氮杂结合位点在γ氨基丁酸受体结合（GABA甲-R）取决于吡唑并喹诺酮核的取代。PCA有助于确定不同的取代基如何促进所研究的PQ的差异行为。使用高架迷宫（EPM）在Wistar成年雄性大鼠中测试了对GABA A -R具有高亲和力的化合物的抗焦虑特性。因此，在N-1（7b - ii和7c- ii）处带有对甲氧基苯基的PQ在低剂量（0.5-1.0 mg / kg）下显示出显着的抗焦虑活性。同时，PQS设有一个未取代的苯基（7B -我）或p
• 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.