ethyl 4-chloro-1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate | 863586-42-9

• 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: ethyl 4-chloro-1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 4-chloro-1-[(4-methoxyphenyl)methyl]-2-oxoquinoline-3-carboxylate
• CAS: 863586-42-9
• 化学式: C₂₀H₁₈ClNO₄
• 分子量: 371.82
• InChiKey: ZLZQNODCXGELOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-chloro-1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate 在 盐酸 、 三氟甲磺酸 、 sodium ethanolate 、 potassium carbonate 、 1-羟基苯并三唑 、 苯甲醚 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 84.84h， 生成 N-[1-(2-hydroxyethyl)piperidin-4-yl]-3-methoxy-1-methyl-4-oxo-5-(2-phenylethyl)pyrrolo[3,2-c]quinoline-2-carboxamide
  参考文献：
  名称：

  Discovery of pyrrolo[3,2-c]quinoline-4-one derivatives as novel hedgehog signaling inhibitors

  摘要：

  The Hedgehog (Hh) signaling pathway plays a significant role in the regulation of cell growth and differentiation during embryonic development. Since activation of the Hh signaling pathway is implicated in several types of human cancers, inhibitors of this pathway could be promising anticancer agents. Using high throughput screening, thieno[3,2-c] quinoline-4-one derivative 9a was identified as a compound of interest with potent in vitro activity but poor metabolic stability. Our efforts focused on enhancement of in vitro inhibitory activity and metabolic stability, including core ring conversion and side chain optimization. This led to the discovery of pyrrolo[3,2-c] quinoline-4-one derivative 12b, which has a structure distinct from previously reported Hh signaling inhibitors. Compound 12b suppressed stromal Gli1 mRNA expression in a murine model and demonstrated antitumor activity in a murine medulloblastoma allograft model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.039
• 作为产物：
  描述：

  2,4-二羟基喹啉-3-甲酸乙酯 在 sodium acetate 、 三氯氧磷 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 7.0h， 生成 ethyl 4-chloro-1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Discovery of pyrrolo[3,2-c]quinoline-4-one derivatives as novel hedgehog signaling inhibitors

  摘要：

  The Hedgehog (Hh) signaling pathway plays a significant role in the regulation of cell growth and differentiation during embryonic development. Since activation of the Hh signaling pathway is implicated in several types of human cancers, inhibitors of this pathway could be promising anticancer agents. Using high throughput screening, thieno[3,2-c] quinoline-4-one derivative 9a was identified as a compound of interest with potent in vitro activity but poor metabolic stability. Our efforts focused on enhancement of in vitro inhibitory activity and metabolic stability, including core ring conversion and side chain optimization. This led to the discovery of pyrrolo[3,2-c] quinoline-4-one derivative 12b, which has a structure distinct from previously reported Hh signaling inhibitors. Compound 12b suppressed stromal Gli1 mRNA expression in a murine model and demonstrated antitumor activity in a murine medulloblastoma allograft model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.039

文献信息

• PYRAZOLOQUINOLONE DERIVATIVE AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1719771A1

  公开（公告）日：2006-11-08

  The present invention provides a pyarzoloquinolone derivative having kinase inhibitory activity. The derivative is represented by the formula: wherein R1 is an aryl group which may be substituted, or an aromatic heterocyclic group which may be substituted; R2 is a hydrogen atom, an amino group which may be substituted, a hydroxy group which may be substituted, or a thiol group which may be substituted; R3, R4, R5 and R6, which may be identical or different, are each (1) a hydrogen atom, (2) a nitro group, (3) a cyano group, (4) a halogen atom, (5) a hydrocarbon group which may be substituted, (6) an amino group which may be substituted, (7) a hydroxy group which may be substituted, or (8) a thiol group which may be substituted; and R3 and R4, R4 and R5, and R5 and R6 may respectively form a ring together with the adjacent carbon atom, or salt thereof.

  本发明提供了一种具有激酶抑制活性的吡唑喹啉衍生物。该衍生物由以下式表示： 其中R1是可以被取代的芳基或可以被取代的芳香杂环基；R2是氢原子、可以被取代的氨基、可以被取代的羟基或可以被取代的硫基；R3、R4、R5和R6，可以相同也可以不同，分别是（1）氢原子、（2）硝基、（3）氰基、（4）卤原子、（5）可以被取代的碳氢基、（6）可以被取代的氨基、（7）可以被取代的羟基或（8）可以被取代的硫基；且R3和R4、R4和R5、以及R5和R6可以分别与相邻的碳原子形成环，或其盐。
• FUSED HETEROCYCLIC DERIVATIVE AND USE THEREOF
  申请人：FUJII Nobuhiro

  公开号：US20090227561A1

  公开（公告）日：2009-09-10

  The present invention provides a compound having a superior Smo inhibitory activity and lower toxicity, which is sufficiently satisfactory as a pharmaceutical product. The present invention provides a compound represented by the formula wherein ring A is 5- to 7-membered ring optionally having substituent(s), where substituents are optionally bonded to each other to form a ring; X is O, S or NR 1 (R 1 is a hydrogen atom or a hydrocarbon group optionally having substituent(s)); R 2 is carbamoyl optionally having substituent(s); and R 3 is hydroxy optionally having substituent(s), or a salt thereof.

  本发明提供了一种具有优异的Smo抑制活性和较低毒性的化合物，该化合物作为药物产品是完全令人满意的。本发明提供了一种由下式表示的化合物： 其中，环A是5-至7-成员环，可选择地具有取代基，其中取代基可选择地与彼此结合形成环；X是O、S或NR1（R1是氢原子或具有取代基的碳氢基团）；R2是氨基甲酰，可选择地具有取代基；R3是羟基，可选择地具有取代基，或其盐。
• Pyrazoloquinolone Derivative And Use Thereof
  申请人：Fukumoto Shojl

  公开号：US20070281963A1

  公开（公告）日：2007-12-06

  The present invention provides a pyarzoloquinolone derivative having kinase inhibitory activity. The derivative is represented by the formula: wherein R 1 is an aryl group which may be substituted, or an aromatic heterocyclic group which may be substituted; R 2 is a hydrogen atom, an amino group which may be substituted, a hydroxy group which may be substituted, or a thiol group which may be substituted; R 3 , R 4 , R 5 and R 6 , which may be identical or different, are each (1) a hydrogen atom, (2) a nitro group, (3) a cyano group, (4) a halogen atom, (5) a hydrocarbon group which may be substituted, (6) an amino group which may be substituted, (7) a hydroxy group which may be substituted, or (8) a thiol group which may be substituted; and R 3 and R 4 , R 4 and R 5 , and R 5 and R 6 may respectively form a ring together with the adjacent carbon atom, or salt thereof.

  本发明提供了一种具有激酶抑制活性的吡唑喹啉衍生物。该衍生物由以下公式表示：其中，R1是可以被取代的芳基或可以被取代的芳香杂环基；R2是氢原子，可以被取代的氨基，可以被取代的羟基或可以被取代的硫醇基；R3、R4、R5和R6可以相同也可以不同，分别是（1）氢原子，（2）硝基，（3）氰基，（4）卤原子，（5）可以被取代的碳氢基，（6）可以被取代的氨基，（7）可以被取代的羟基或（8）可以被取代的硫醇基；R3和R4，R4和R5，以及R5和R6可以分别与相邻的碳原子形成环，或其盐。
• US7842701B2
  申请人：——

  公开号：US7842701B2

  公开（公告）日：2010-11-30
• US8217176B2
  申请人：——

  公开号：US8217176B2

  公开（公告）日：2012-07-10