4-(5-carboxy-2-benzimidazolyl)-3-(4-chlorophenyl)butanoic acid hydrochloride | 1221961-95-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 4-(5-carboxy-2-benzimidazolyl)-3-(4-chlorophenyl)butanoic acid hydrochloride
• 英文别名: 4-(5-carboxy-2-benzimidazolyl)-3-(4-chlorophenyl)butanoic acid.HCl；2-[3-carboxy-2-(4-chlorophenyl)propyl]-3H-benzimidazole-5-carboxylic acid;hydrochloride
• CAS: 1221961-95-0
• 化学式: C₁₈H₁₅ClN₂O₄*ClH
• 分子量: 395.242
• InChiKey: VRJBOTGCOCGVBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.14
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(4-氯苯基)戊二酸 在 盐酸 、 溶剂黄146 、 乙酰氯 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 生成 4-(5-carboxy-2-benzimidazolyl)-3-(4-chlorophenyl)butanoic acid hydrochloride
  参考文献：
  名称：

  4-Benzimidazolyl-3-Phenylbutanoic Acids As Novel Pif-Pocket-Targeting Allosteric Inhibitors of Protein Kinase PKCζ

  摘要：

  Protein kinase inhibitors with an allosteric mode of action are expected to reach, in many cases, higher selectivity for the target enzyme than ATP-competitive compounds. Therefore, basic research is aiming at identifying and establishing novel sites on the catalytic domain of protein kinases which might be targeted by allosteric inhibitors. We previously published the first structure-activity relationships (SARs) for allosteric activators of protein kinase PDK1. Here, we present the design, synthesis, and SAR data on a series of novel compounds, 4-benzimidazolyl-3-phenylbutanoic acids, that inhibit the atypical protein kinace C (PKC) zeta via binding to the PIF-pocket. Key positions were identified in the compounds that can be modified to increase potency and selectivity. Some congeners showed a high selectivity toward PKC zeta, lacking inhibition of the most closely related isoform, PKCl, and of further AGC kinases. Furthermore, evidence is provided that these compounds are also active toward cellular PKC zeta without loss of potency compared to the cell-free assay.

  DOI：

  10.1021/jm2005892

文献信息

• ALLOSTERIC PROTEIN KINASE MODULATORS
  申请人：Engel Matthias

  公开号：US20120046307A1

  公开（公告）日：2012-02-23

  The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.

  本发明提供了特定的小分子化合物，它们通过变构调节AGC蛋白激酶的活性或调节Aurora家族蛋白激酶的蛋白质-蛋白质相互作用，其生产方法，包含该化合物的药物组合物，以及它们用于制备治疗和预防与AGC蛋白激酶或Aurora家族蛋白激酶异常活动相关疾病的药物的应用。
• Allosteric protein kinase modulators
  申请人：Engel Matthias

  公开号：US08912186B2

  公开（公告）日：2014-12-16

  The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.

  本发明提供了一种特定的小分子化合物，可以变构地调节AGC蛋白激酶和Aurora家族蛋白激酶的活性或调节它们之间的蛋白质相互作用，以及制备它们的方法、包含它们的制药组合物，以及它们用于制备治疗与AGC蛋白激酶或Aurora家族蛋白激酶异常活性相关的疾病的药物。
• US8912186B2
  申请人：——

  公开号：US8912186B2

  公开（公告）日：2014-12-16
• 4-Benzimidazolyl-3-Phenylbutanoic Acids As Novel Pif-Pocket-Targeting Allosteric Inhibitors of Protein Kinase PKCζ
  作者：Wolfgang Fröhner、Laura A. Lopez-Garcia、Sonja Neimanis、Nadja Weber、Jeanette Navratil、Frauke Maurer、Adriana Stroba、Hua Zhang、Ricardo M. Biondi、Matthias Engel

  DOI：10.1021/jm2005892

  日期：2011.10.13

  Protein kinase inhibitors with an allosteric mode of action are expected to reach, in many cases, higher selectivity for the target enzyme than ATP-competitive compounds. Therefore, basic research is aiming at identifying and establishing novel sites on the catalytic domain of protein kinases which might be targeted by allosteric inhibitors. We previously published the first structure-activity relationships (SARs) for allosteric activators of protein kinase PDK1. Here, we present the design, synthesis, and SAR data on a series of novel compounds, 4-benzimidazolyl-3-phenylbutanoic acids, that inhibit the atypical protein kinace C (PKC) zeta via binding to the PIF-pocket. Key positions were identified in the compounds that can be modified to increase potency and selectivity. Some congeners showed a high selectivity toward PKC zeta, lacking inhibition of the most closely related isoform, PKCl, and of further AGC kinases. Furthermore, evidence is provided that these compounds are also active toward cellular PKC zeta without loss of potency compared to the cell-free assay.