1-(3-quinolinyl)-indol-3-yl glyoxylic methyl ester | 436161-53-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(3-quinolinyl)-indol-3-yl glyoxylic methyl ester
• 英文别名: Methyl 2-oxo-2-(1-quinolin-3-ylindol-3-yl)acetate
• CAS: 436161-53-4
• 化学式: C₂₀H₁₄N₂O₃
• 分子量: 330.343
• InChiKey: QTQZZPJZXDBOIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)acetamide 、 1-(3-quinolinyl)-indol-3-yl glyoxylic methyl ester 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以77%的产率得到3-[1-(3-Dimethylamino-propyl)-1H-indazol-3-yl]-4-(1-quinolin-3-yl-1H-indol-3-yl)-pyrrole-2,5-dione
  参考文献：
  名称：

  Novel Indolylindazolylmaleimides as Inhibitors of Protein Kinase C-β:  Synthesis, Biological Activity, and Cardiovascular Safety

  摘要：

  Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3 beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-beta II (IC50 = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs.

  DOI：

  10.1021/jm049478u
• 作为产物：
  描述：

  3-溴喹啉 在 potassium carbonate 、 copper(II) oxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 1-(3-quinolinyl)-indol-3-yl glyoxylic methyl ester
  参考文献：
  名称：

  Novel Indolylindazolylmaleimides as Inhibitors of Protein Kinase C-β:  Synthesis, Biological Activity, and Cardiovascular Safety

  摘要：

  Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3 beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-beta II (IC50 = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs.

  DOI：

  10.1021/jm049478u

文献信息

• Indazolyl-substituted pyrroline compounds as kinase inhibitors
  申请人：——

  公开号：US20030055097A1

  公开（公告）日：2003-03-20

  The present invention is directed to novel indazolyl-substituted pyrroline compounds of Formula (I): 1 useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.

  本发明涉及一种新型的Formula (I)的吲哚基取代吡咯烯化合物，可用作激酶或双重激酶抑制剂，生产这种化合物的方法以及用于治疗或改善激酶或双重激酶介导的疾病的方法。
• [EN] BISINDOLYL-MALEIMID DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DERIVES DE BISINDOLYL-MALEIMIDE UTILISES EN TANT QU'INHIBITEURS DE KINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2003104222A1

  公开（公告）日：2003-12-18

  The present invention is directed to novel substituted pyrroline compounds of Formula (I) wherein R1 is selected from the group consisting of a pyridinyl-R5, pyrimidinyl-R5, pyrazinyl-R5, furyl-R5, thienyl-R5, benzofuryl-R5, benzothienyl-R5, quinolinyl-R5 and isoquinolinyl-R5 ring attached to the indole nitrogen atom via a ring carbon atom;useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder such as cardiovascular, inflammatory, immunological, dermatological, oncological, CNS disorders and diabetes.

  本发明涉及一种新的取代吡咯烷化合物，其化学式为（I），其中R1选自以下组中的一种：连接到吲哚氮原子上的环碳原子的吡啶基-R5，嘧啶基-R5，吡嗪基-R5，呋喃基-R5，噻吩基-R5，苯并呋喃基-R5，苯并噻吩基-R5，喹啉基-R5和异喹啉基-R5环；作为激酶或双重激酶抑制剂，制备这种化合物的方法以及治疗或改善激酶或双重激酶介导的疾病的方法，如心血管疾病、炎症、免疫、皮肤、肿瘤、中枢神经系统疾病和糖尿病。
• INDAZOLYL-SUBSTITUTED PYRROLINE COMPOUNDS AS KINASE INHIBITORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1362047A2

  公开（公告）日：2003-11-19
• BISINDOLYL-MALEIMID DERIVATIVES AS KINASE INHIBITORS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1513830A1

  公开（公告）日：2005-03-16
• Substituted pyrrolines as kinase inhibitors
  申请人：——

  公开号：US20040059113A1

  公开（公告）日：2004-03-25

  The present invention is directed to novel substituted pyrroline compounds useful as kinase or dual-kinase inhibitors, methods for producing such compounds and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.