3-[1-(3-hydroxypropyl)-1H-indazol-3-yl]-4-[1-(2-naphthalenyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione | 436161-15-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[1-(3-hydroxypropyl)-1H-indazol-3-yl]-4-[1-(2-naphthalenyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione
• 英文别名: 3-[1-(3-hydroxy-propyl)-1H-indazol-3-yl]-4-(1-naphthalen-2-yl-1H-indol-3-yl)-pyrrole-2,5-dione；3-[1-(3-hydroxypropyl)indazol-3-yl]-4-(1-naphthalen-2-ylindol-3-yl)pyrrole-2,5-dione
• CAS: 436161-15-8
• 化学式: C₃₂H₂₄N₄O₃
• 分子量: 512.568
• InChiKey: DHCJBUBNHLTJRM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  89.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[1-(3-hydroxypropyl)-1H-indazol-3-yl]-4-[1-(2-naphthalenyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione 在 吡啶 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 5.0h， 生成 3-[1-(2-naphthalenyl)-1H-indol-3-yl]-4-[1-[3-(1-pyrrolidinyl)propyl]-1H-indazol-3-yl]-1H-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：

  1-(2-Naphthalenyl)-I+/--oxo-1H-indole-3-acetyl chloride 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.67h， 生成 3-[1-(3-hydroxypropyl)-1H-indazol-3-yl]-4-[1-(2-naphthalenyl)-1H-indol-3-yl]-1H-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

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。
• Substituted indazolyl(indolyl)maleimide derivatives as kinase inhibitors
  申请人：Zhang Han-Cheng

  公开号：US20050004201A1

  公开（公告）日：2005-01-06

  The present invention is directed to novel indazolyl-substituted pyrroline compounds of Formula (I): R 2 is selected from the group consisting of —C 1-8 alkyl-Z, —C 2-8 alkenyl-Z and —C 2-8 alkynyl-Z; wherein the —C 1-8 alkyl-Z, —C 2-8 alkenyl-Z and —C 2-8 alkynyl-Z and Z is a 5 to 6 member aromatic monocyclic heteroaryl ring having from 2 to 4 heteroatoms. These compounds are 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)的吲唑基取代的吡咯烯化合物：R2选自由—C1-8烷基-Z，—C2-8烯基-Z和—C2-8炔基-Z组成的群；其中—C1-8烷基-Z，—C2-8烯基-Z和—C2-8炔基-Z以及Z是一个含有2到4个杂原子的5到6成员芳香单环杂环烷基环。这些化合物可用作激酶或双激酶抑制剂，用于生产这种化合物的方法以及治疗或改善激酶或双激酶介导的疾病的方法。
• INDAZOLYL-SUBSTITUTED PYRROLINE COMPOUNDS AS KINASE INHIBITORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1362047B1

  公开（公告）日：2006-05-17
• US6849643B2
  申请人：——

  公开号：US6849643B2

  公开（公告）日：2005-02-01
• US7304060B2
  申请人：——

  公开号：US7304060B2

  公开（公告）日：2007-12-04