4-((2,4-dichlorophenyl)amino)-6,7-dimethoxyquinoline-3-carbonitrile | 331662-50-1

• 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
• 英文名称: 4-((2,4-dichlorophenyl)amino)-6,7-dimethoxyquinoline-3-carbonitrile
• 英文别名: 4-(2,4-dichlorophenylamino)-6,7-dimethoxyquinoline-3-carbonitrile；4-(2,4-dichloroanilino)-6,7-dimethoxyquinoline-3-carbonitrile；4-[(2,4-Dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile
• CAS: 331662-50-1
• 化学式: C₁₈H₁₃Cl₂N₃O₂
• 分子量: 374.226
• InChiKey: IUZCVUGIDCZCEQ-UHFFFAOYSA-N

物化性质

• 熔点：
  243-244 °C
• 沸点：
  502.2±50.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-((2,4-dichlorophenyl)amino)-6,7-dimethoxyquinoline-3-carbonitrile 在 吡啶 、 4-二甲氨基吡啶 、 吡啶盐酸盐 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 3-Quinolinecarbonitrile deriv. 2i
  参考文献：
  名称：

  Synthesis and Src Kinase Inhibitory Activity of a Series of 4-Phenylamino-3-quinolinecarbonitriles

  摘要：

  Screening of a directed compound library in a yeast-based assay identified 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (2a) as a Src inhibitor. An enzymatic assay established that 2a was an ATP-competitive inhibitor of the kinase activity of Src. We present here SAR data for 2a which shows that the aniline group at C-4, the carbonitrile group at C-3, and the alkoxy groups at C-6 and C-7 of the quinoline are crucial for optimal activity. Increasing the size of the C-2 substituent of the aniline at C-4 of 2a from chloro to bromo to iodo resulted in a corresponding increase in Src inhibition. Furthermore, replacement of the 7-methoxy group of 2a with various 3-heteroalkylaminopropoxy groups provided increased inhibition of both Src enzymatic and cellular activity. Compound 25, which contains a 3-morpholinopropoxy group, had an IC50 of 3.8 nM in the Src enzymatic assay and an IC50 of 940 nM for the inhibition of Src-dependent cell proliferation.

  DOI：

  10.1021/jm000420z
• 作为产物：
  描述：

  4-羟基-6,7-二甲氧基-3-喹啉甲腈 在 sodium hydride 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.0h， 生成 4-((2,4-dichlorophenyl)amino)-6,7-dimethoxyquinoline-3-carbonitrile
  参考文献：
  名称：

  Discovery of Multitarget Antivirals Acting on Both the Dengue Virus NS5-NS3 Interaction and the Host Src/Fyn Kinases

  摘要：

  This study describes the discovery of novel dengue virus inhibitors targeting both a crucial viral protein protein interaction and an essential host cell factor as a strategy to reduce the emergence of drug resistance. Starting from known c-Src inhibitors, a virtual screening was performed to identify molecules able to interact with a recently discovered allosteric pocket on the dengue virus NS5 polymerase. The selection of cheap-to-produce scaffolds and the exploration of the biologically relevant chemical space around them suggested promising candidates for chemical synthesis. A series of purines emerged as the most interesting candidates able to inhibit virus replication at low micromolar concentrations with no Significant toxicity to the host cell. Among the identified antivirals, compound 16i proved to be 10 times More potent than ribavirin, showed a better selectivity index and represents the first-in-class DENV-NS5 allosteric inhibitor able to target both the virus NS5-NS3 interaction and the host kinases c-Src/Fyn.

  DOI：

  10.1021/acs.jmedchem.5b00108

文献信息

• [EN] QUINOLINE COMPOUNDS FOR INCREASING INSULINE RELEASE<br/>[FR] COMPOSÉS DE QUINOLÉINE POUR AUGMENTER LA LIBÉRATION D'INSULINE
  申请人：MAX-PLANCK-GESELLSCHAFT ZUR FÖRDERUNG DER WSS E V

  公开号：WO2017198756A1

  公开（公告）日：2017-11-23

  The present invention relates to a class of quinoline compounds that act as insulin secretagogues, i.e., induce insulin secretion from beta cells. The present compounds may be used to induce divalent calcium cation influx in pancreatic beta-cells or to activate voltage-dependent calcium channels in pancreatic beta-cells. The present invention further relates to compounds for use in the treatment of diabetes.

  本发明涉及一类喹啉化合物，其作为胰岛素分泌素，即从β细胞中诱导胰岛素分泌。本化合物可用于诱导胰岛β细胞中的二价钙阳离子通量或激活胰岛β细胞中的电压依赖性钙通道。本发明还涉及用于治疗糖尿病的化合物。
• QUINOLINE COMPOUNDS FOR INCREASING INSULINE RELEASE
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP3246028A1

  公开（公告）日：2017-11-22

  The present invention relates to a class of quinoline compounds that act as insulin secretagogues, i.e., induce insulin secretion from beta cells. The present compounds may be used to induce divalent calcium cation influx in pancreatic beta-cells or to activate voltage-dependent calcium channels in pancreatic beta-cells. The present invention further relates to compounds for use in the treatment of diabetes.

  本发明涉及一类可作为胰岛素促泌剂，即诱导β细胞分泌胰岛素的喹啉化合物。本发明化合物可用于诱导胰腺β细胞中的二价钙阳离子流入或激活胰腺β细胞中的电压依赖性钙通道。本发明进一步涉及用于治疗糖尿病的化合物。
• Method of treatment of myocardial infarction
  申请人：——

  公开号：US20040214836A1

  公开（公告）日：2004-10-28

  Myocardial infarction in a mammal is treated by administering to the mammal a therapeutically effective amount of a chemical Src family tyrosine kinase protein inhibitor and the use of such inhibitor compounds for the preparation of a medicament for treating myocardial infarction. Myocardial infarction can be prevented by administering to the mammal a prophylactic amount of the inhibitor. The inhibitor preferably is an inhibitor of Src protein selected from the group consisting of a pyrazolopyrimidine class Src family tyrosine kinase inhibitor, a macrocyclic dienone class Src family tyrosine kinase inhibitor, a pyrido[2,3-d]pyrimidine class Src family tyrosine kinase inhibitor, a 4-anilino-3-quinolinecarbonitrile class Src family tyrosine kinase inhibitor, and a mixture thereof. In a particularly preferred embodiment, the Src family tyrosine kinase inhibitor is an ATP-competitive Src family tyrosine kinase inhibitor having a hydrophobic group that is less than about 6 angstroms in size situated adjacent to an ATP-mimicing heteroaromatic moiety. The Src family tyrosine kinase inhibitors can be used to prepare medicaments for the treatment of myocardial infarction. Also disclosed are articles of manufacture containing a chemical Src family tyrosine kinase inhibitor.

  通过向哺乳动物施用治疗有效量的化学Src家族酪氨酸激酶蛋白抑制剂和使用这种抑制剂化合物制备治疗心肌梗塞的药物，可以治疗哺乳动物的心肌梗塞。向哺乳动物施用预防量的抑制剂可预防心肌梗塞。该抑制剂优选为选自吡唑嘧啶类Src家族酪氨酸激酶抑制剂、大环二烯酮类Src家族酪氨酸激酶抑制剂、吡啶[2,3-d]嘧啶类Src家族酪氨酸激酶抑制剂、4-苯胺基-3-喹啉甲腈类Src家族酪氨酸激酶抑制剂及其混合物组成的组的Src蛋白抑制剂。在一个特别优选的实施方案中，Src 家族酪氨酸激酶抑制剂是一种 ATP 竞争性 Src 家族酪氨酸激酶抑制剂，其疏水基团的大小小于约 6 埃，与 ATP 拟合杂芳香族分子相邻。Src家族酪氨酸激酶抑制剂可用于制备治疗心肌梗塞的药物。还公开了含有化学Src家族酪氨酸激酶抑制剂的制造品。
• Preparation of Heteroaryloxetanes and Heteroarylazetidines by Use of a Minisci Reaction
  作者：Matthew A. J. Duncton、M. Angels Estiarte、Russell J. Johnson、Matthew Cox、Donogh J. R. O’Mahony、William T. Edwards、Michael G. Kelly

  DOI：10.1021/jo9010624

  日期：2009.8.21

  Introduction of oxetan-3-yl and azetidin-3-yl groups into heteroaromatic bases was achieved by using a radical addition method (Minisci reaction). To demonstrate utility. the process was used to introduce an oxetane Or azetidine into heteroaromatic systems that have found important uses in the drug discovery industry, such as the marketed EGFR inhibitor geftinib, a quinolinecarbonitrile Src tyrosine kinase inhibitor, and the antimalarial hydroquinine.
• METHOD OF TREATMENT OF MYOCARDIAL INFARCTION
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：EP1744735A2

  公开（公告）日：2007-01-24