PZ09 | 1132609-87-0

• 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: PZ09
• 英文别名: 4-(3-(4-(4-Methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-indazol-6-yl)aniline；4-{3-[7-(4-Methylpiperazin-1-Yl)-1h-Benzimidazol-2-Yl]-1h-Indazol-6-Yl}aniline；4-[3-[4-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-6-yl]aniline
• CAS: 1132609-87-0
• 化学式: C₂₅H₂₅N₇
• 分子量: 423.52
• InChiKey: LPSCCOBGZSKECZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl 6-(4-aminophenyl)-3-(1-(tert-butoxycarbonyl)-4-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-1H-indazole-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 PZ09
  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

• Composition for Prevention or Treatment of Heart Failure
  申请人：Park Woo Jin

  公开号：US20110245179A1

  公开（公告）日：2011-10-06

  Provided are a composition for preventing or treating heart failure and a method for screening an agent for treating heart failure. The present disclosure demonstrates for the first time that administration of PKCζ inhibitor provides inotropic effect by increasing myocardial contractility. Thus, the present disclosure will contribute greatly to the prevention or treatment of heart failure. Also, since the present disclosure is based on the change in calcium sensitivity in cardiac myocytes unlike the existing inotropic agents, it can enhance the myocardial contractility without increasing oxygen demand or the risk of arrhythmia.

  提供了一种预防或治疗心力衰竭的组合物以及一种筛选治疗心力衰竭药物的方法。本公开首次证明了PKCζ抑制剂的给药通过增加心肌收缩力提供正性肌力作用。因此，本公开将极大地有助于预防或治疗心力衰竭。此外，由于本公开基于心肌细胞中钙敏感性的变化，不同于现有的正性肌力药物，它可以增强心肌收缩力而不增加氧需求或心律失常的风险。
• 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.
• US9301965B2
  申请人：——

  公开号：US9301965B2

  公开（公告）日：2016-04-05
• 2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: Design and synthesis of a potent and isoform selective PKC-ζ inhibitor
  作者：John I. Trujillo、James R. Kiefer、Wei Huang、Atli Thorarensen、Li Xing、Nicole L. Caspers、Jacqueline E. Day、Karl J. Mathis、Kuniko K. Kretzmer、Beverley A. Reitz、Robin A. Weinberg、Roderick A. Stegeman、Ann Wrightstone、Lori Christine、Robert Compton、Xiong Li

  DOI：10.1016/j.bmcl.2008.11.105

  日期：2009.2

  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).