3-[4-(4-Methylpiperazin-1-yl)-1H-benzoimidazol-2-yl]-6-(2-methoxy-4-hydroxyphenyl)-1H-indazole | 319461-75-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-[4-(4-Methylpiperazin-1-yl)-1H-benzoimidazol-2-yl]-6-(2-methoxy-4-hydroxyphenyl)-1H-indazole
• 英文别名: Indazole-benzimidazole, 1；3-methoxy-4-[3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-6-yl]phenol
• CAS: 319461-75-1
• 化学式: C₂₆H₂₆N₆O₂
• 分子量: 454.531
• InChiKey: RQXOBAMSPDGWSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  93.3
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl 3-(1-(tert-butoxycarbonyl)-4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-6-(4-hydroxy-2-methoxyphenyl)-1H-indazole-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 3-[4-(4-Methylpiperazin-1-yl)-1H-benzoimidazol-2-yl]-6-(2-methoxy-4-hydroxyphenyl)-1H-indazole
  参考文献：
  名称：

  2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: Design and synthesis of a potent and isoform selective PKC-ζ inhibitor

  摘要：

  The inhibition of PKC-zeta has been proposed to be a potential drug target for immune and inflammatory diseases. A series of 2-(6-phenyl-1H indazol-3-yl)-1H-benzo[d]imidazoles with initial high crossover to CDK-2 has been optimized to afford potent and selective inhibitors of protein kinase c-zeta (PKC-zeta). The determination of the crystal structures of key inhibitor:CDK-2 complexes informed the design and analysis of the series. The most selective and potent analog was identified by variation of the aryl substituent at the 6-position of the indazole template to give a 4-NH(2) derivative. The analog displays good selectivity over other PKC isoforms (alpha, betaII, gamma, delta, epsilon, mu, theta, eta and iota/lambda) and CDK-2, however it displays marginal selectivity against a panel of other kinases (37 profiled).

  DOI：

  10.1016/j.bmcl.2008.11.105

文献信息

• INDAZOLE COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR INHIBITING PROTEIN KINASES, AND METHODS FOR THEIR USE
  申请人：——

  公开号：US20040220248A1

  公开（公告）日：2004-11-04

  Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

  本文介绍了调节和/或抑制某些蛋白激酶活性的吲唑类化合物。这些化合物及含有它们的药物组合物能够介导酪氨酸激酶信号转导，从而调节和/或抑制不必要的细胞增殖。本发明还涉及含有这些化合物的药物组合物的治疗或预防用途，以及通过给予有效量的这些化合物来治疗癌症和其他与不必要的血管生成和/或细胞增殖相关的疾病状态，如糖尿病视网膜病变、新生血管性青光眼、类风湿性关节炎和牛皮癣的方法。
• Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
  申请人：Kania Steven Robert

  公开号：US20050124662A1

  公开（公告）日：2005-06-09

  Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

  本文描述了调节和/或抑制某些蛋白激酶活性的吲唑化合物。这些化合物及含有它们的药物组成物能够介导酪氨酸激酶信号转导，从而调节和/或抑制不必要的细胞增殖。本发明还涉及含有这种化合物的药物组成物的治疗或预防用途，并通过给予有效剂量的这种化合物的方法来治疗癌症和与不必要的血管生成和/或细胞增殖有关的其他疾病状态，例如糖尿病视网膜病变、新生血管性青光眼、类风湿性关节炎和银屑病。
• Compositions and methods for establishing and maintaining stem cells in an undifferentiated state
  申请人：Paul Soumen

  公开号：US20100317100A1

  公开（公告）日：2010-12-16

  The present invention embraces compositions and methods for establishing and maintaining stem cells and inhibiting stem cell differentiation using a selective Protein Kinase C (PKC) inhibitor.
• Compositions and Methods for Establishing and Maintaining Stem Cells in an Undiffferentiated State
  申请人：Paul Soumen

  公开号：US20120270313A1

  公开（公告）日：2012-10-25

  The present invention embraces compositions and methods for establishing and maintaining stem cells and inhibiting stem cell differentiation using a selective Protein Kinase C (PKC) inhibitor.
• METHOD OF TREATING OVARIAN CANCER USING A PKC INHIBITOR
  申请人：Acevedo-Duncan Mildred Enid

  公开号：US20150366883A1

  公开（公告）日：2015-12-24

  A method of treating ovarian cancer by administering a PKC inhibitor is presented herein. It was found that administering a PKC inhibitor, such as ACPD or ICA-1, to ovarian cancer cells inhibited cancer cell proliferation.