4-chloro-2-methylquinoline-3-carboxylic acid ethyl ester | 50593-70-9

• 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: 4-chloro-2-methylquinoline-3-carboxylic acid ethyl ester
• 英文别名: ethyl 4-chloro-2-methyl-3-quinolinecarboxylate；ethyl 4-chloro-2-methylquinoline-3-carboxylate；Ethyl 4-chloro-2-methyl-quinoline-3-carboxylate；ethyl 4-chloro-2-methylquinolin-3-carboxylate
• CAS: 50593-70-9
• 化学式: C₁₃H₁₂ClNO₂
• 分子量: 249.697
• InChiKey: UASKCSYIRXPZPX-UHFFFAOYSA-N

物化性质

• 沸点：
  330.6±37.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 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：

  4-chloro-2-methylquinoline-3-carboxylic acid ethyl ester 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 22.0h， 以34%的产率得到2-(溴甲基)-4-氯喹啉-3-羧酸乙酯
  参考文献：
  名称：

  基于吡咯烷酮结构的新型有效的5-HT（3）受体配体：合成，生物学评估和配体-受体相互作用方式的计算合理化。

  摘要：

  设计并合成了新型5-HT（3）受体拮抗剂的新型构象受约束的衍生物，旨在以系统的方式探测中央5-HT（3）受体识别位点。测试了新合成的化合物在大鼠皮膜中抑制[（3）H]格兰司琼对5-HT（3）受体的特异性结合的潜在能力。这些研究揭示了一些正在研究的化合物的亚纳摩尔亲和力。发现该系列中最有效的配体是喹核苷衍生物（S）-7i，其显示出与参考配体格拉司琼相当的亲和力。在体外对NG 108-15细胞中的5-HT（3）受体依赖性[（14）C]胍鎓摄取进行了评估，对某些选定化合物的潜在5-HT（3）激动剂/拮抗剂活性进行了评估。在此功能测定中测试的两种托烷衍生物（7a和9a）均表现出拮抗特性，而研究的喹uc啶衍生物[化合物7i，8g和9g的对映体以及化合物（R）-8h]则显示了全部内在功效。因此，这些5-HT（3）受体配体的功能行为似乎受氮杂双环部分和杂芳族部分的结构特征影响。与在NG 108-15细胞

  DOI：

  10.1016/s0968-0896(01)00332-7
• 作为产物：
  描述：

  2-(1-(苯基氨基)亚乙基)丙二酸二乙酯 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 二苯醚 为溶剂， 反应 2.0h， 生成 4-chloro-2-methylquinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

  摘要：

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

  DOI：

  10.1021/jm060262x

文献信息

• Pyrazoloquinolines
  申请人：Ciba-Geigy Corporation

  公开号：US04312870A1

  公开（公告）日：1982-01-26

  2-Aryl-pyrazolo[4-3-c]quinolin-3-ones, e.g. those of the formula ##STR1## and pharmaceutically acceptable acyl derivatives or salts thereof, are psychoactive agents useful in the treatment of anxiety or depression.

  2-芳基吡唑并[4-3-c]喹啉-3-酮，例如式##STR1##及其药用可接受的酰基衍生物或盐，是用于治疗焦虑或抑郁的精神活性剂。
• Synthesis of new pyrazolo[4,3-<i>c</i>]quinolin-3-one derivatives and some oxazolo[4,5-<i>c</i>]quinoline-2,4-diones
  作者：Lhassane Ismaïli、Bernard Refouvelet、Jean François Robert

  DOI：10.1002/jhet.5570360323

  日期：1999.5

  The new pyrazolo[4,3-c]quinolin-3-one derivatives 3a-c and 6a-c were prepared by the following three steps: first the preparation of ethyl 4-hydroxyquinoline-3-carboxylate derivatives 1 and 4 by reaction of isatoic anhydrides and ethyl malonate and ethyl acetoacetate respectively, then chloration of 1 and 4 with phosphorus oxychloride to give 2 and 5 and finally the condensation of 2 and 5 with hydrazine

  通过以下三个步骤制备新的吡唑并[4，3 - c ]喹啉-3-酮衍生物3a-c和6a-c：首先通过与下列物质的反应制备4-羟基喹啉-3-羧酸乙酯衍生物1和4。分别用二酸酐，丙二酸乙酯和乙酰乙酸乙酯，然后用氯氧化磷将1和4氯化，得到2和5，最后将2和5与肼及其衍生物缩合。此外，成功合成了恶唑并[4,5 - c ]喹啉-2,4-二酮9a-f 被报道。
• Discovery of Plasmodium vivax<i>N</i>-Myristoyltransferase Inhibitors: Screening, Synthesis, and Structural Characterization of their Binding Mode
  作者：Victor Goncalves、James A. Brannigan、David Whalley、Keith H. Ansell、Barbara Saxty、Anthony A. Holder、Anthony J. Wilkinson、Edward W. Tate、Robin J. Leatherbarrow

  DOI：10.1021/jm300040p

  日期：2012.4.12

  N-Myristoyltransferase (NMT) is a prospective drug target against parasitic protozoa. Herein we report the successful discovery of a series of Plasmodium vivax NMT inhibitors by high-throughput screening. A high-resolution crystal structure of the hit compound in complex with NMT was obtained, allowing understanding of its novel binding mode. A set of analogues was designed and tested to define the

  N-肉豆蔻酰转移酶 (NMT) 是一种针对寄生原生动物的前瞻性药物靶点。在此，我们报告通过高通量筛选成功发现了一系列间日疟原虫NMT 抑制剂。获得了与 NMT 复合的命中化合物的高分辨率晶体结构，从而可以了解其新的结合模式。设计并测试了一组类似物以定义与活性和选择性相关的化学基团。
• THERAPEUTIC PYRAZOLOQUINOLINE UREA DERIVATIVES
  申请人：Kaplan Alan P.

  公开号：US20080306048A1

  公开（公告）日：2008-12-11

  The invention provides a novel chemical series of formula I, as well as methods of use thereof for binding to the benzodiazepine site of the GABA A receptor and modulating GABA A , and use of the compound of formula I for the treatment of GABA A receptor associated disorders. The general structure of formula I is shown below: The invention further provides a method of modulation of one or more GABA A subtypes in an animal comprising administering to the animal an effective amount of a compound of formula (I).

  该发明提供了一种新的化学系列，其化学式为I，以及使用该系列的方法，用于结合到GABAA受体的苯二氮卓位点并调节GABAA，并且使用化合物I的化学式进行治疗GABAA受体相关疾病。化学式I的一般结构如下所示：该发明还提供了一种调节动物体内一个或多个GABAA亚型的方法，包括向动物投与化学式(I)化合物的有效量。
• Therapeutic pyrazoloquinoline urea derivatives
  申请人：Helicon Therapeutics, Inc.

  公开号：US07863266B2

  公开（公告）日：2011-01-04

  The invention provides a novel chemical series of formula I, as well as methods of use thereof for binding to the benzodiazepine site of the GABAA receptor and modulating GABAA, and use of the compound of formula I for the treatment of GABAA receptor associated disorders. The general structure of formula I is shown below: The invention further provides a method of modulation of one or more GABAA subtypes in an animal comprising administering to the animal an effective amount of a compound of formula (I).

  本发明提供了一种新的化学系列，其化学式为I，并提供了使用该化合物结合到GABAA受体的苯二氮平位点和调节GABAA的方法，以及使用化合物I的方法治疗GABAA受体相关疾病。化合物I的一般结构如下所示： 本发明还提供了一种调节动物体内一种或多种GABAA亚型的方法，包括向动物体内投与化合物I的有效量。