3-(4-tert-butylphenyl)glutaric anhydride | 185049-55-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-tert-butylphenyl)glutaric anhydride
• 英文别名: 3-(4-t-butylphenyl)glutaric anhydride；2H-Pyran-2,6(3H)-dione, 4-[4-(1,1-dimethylethyl)phenyl]dihydro-；4-(4-tert-butylphenyl)oxane-2,6-dione
• CAS: 185049-55-2
• 化学式: C₁₅H₁₈O₃
• 分子量: 246.306
• InChiKey: RCDUMUKBCQLEHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-tert-butylphenyl)glutaric anhydride 在 1-[3-(diethylamino)propyl]-3-ethylcarbodiimide hydrochloride 、 对甲苯磺酸 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-[[3-(4-tert-butylphenyl)-5-[[(3S,5S,8R,9S,10S,13S,14S,17S)-17-[3-(4-tert-butylphenyl)-5-oxo-5-(2-sulfoethylamino)pentanoyl]oxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-5-oxopentanoyl]amino]ethanesulfonic acid
  参考文献：
  名称：

  人工细胞色素p-450酶催化甾体底物的氧化。

  摘要：

  包含带有环糊精结合基团的锰-卟啉的催化剂能够以底物选择性，区域和立体选择性以及高催化转化率进行羟基化。催化剂/底物配合物的几何形状超越了固有的底物反应性，从而允许在存在仲甲醇基团和碳-碳双键的情况下，如在酶促反应中，攻击类固醇的几何可及的饱和碳。甾族碳9位的选择性羟基化特别实用。

  DOI：

  10.1021/jo020174u
• 作为产物：
  描述：

  对叔丁基苯甲醛 在 四氢吡咯 、 乙酸酐 作用下， 以 乙醇 为溶剂， 反应 27.0h， 生成 3-(4-tert-butylphenyl)glutaric anhydride
  参考文献：
  名称：

  人工细胞色素p-450酶催化甾体底物的氧化。

  摘要：

  包含带有环糊精结合基团的锰-卟啉的催化剂能够以底物选择性，区域和立体选择性以及高催化转化率进行羟基化。催化剂/底物配合物的几何形状超越了固有的底物反应性，从而允许在存在仲甲醇基团和碳-碳双键的情况下，如在酶促反应中，攻击类固醇的几何可及的饱和碳。甾族碳9位的选择性羟基化特别实用。

  DOI：

  10.1021/jo020174u

文献信息

• [EN] ALLOSTERIC PROTEIN KINASE MODULATORS<br/>[FR] MODULATEURS DE PROTÉINE KINASE ALLOSTÉRIQUE
  申请人：UNIV SAARLAND

  公开号：WO2010043711A1

  公开（公告）日：2010-04-22

  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.

  该发明提供特定的小分子化合物，这些化合物能够变构调节AGC蛋白激酶的活性或调节Aurora家族蛋白激酶的蛋白-蛋白相互作用，提供这些化合物的制备方法，包含这些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：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。
• Biomimetic hydroxylation of saturated carbons with artificial cytochrome P-450 enzymes—liberating chemistry from the tyranny of functional groups
  作者：Ronald Breslow、Jerry Yang、Jiaming Yan

  DOI：10.1016/s0040-4020(01)01098-5

  日期：2002.1

  Five mimics of cytochrome P-450 have been prepared and examined as catalysts for the specific hydroxylation of steroids. Reactions occur dictated by the geometries of the complexes, overcoming the intrinsic reactivity of a carbon–carbon double bond and of a secondary carbinol group. In some cases as many as 3000 catalytic turnovers are observed.

  已经制备了五种细胞色素P-450的模拟物，并作为类固醇特异性羟基化的催化剂进行了检测。反应的发生取决于配合物的几何形状，克服了碳-碳双键和仲甲醇基团的固有反应性。在某些情况下，观察到多达3000次催化转化。
• Allosteric protein kinase modulators
  申请人：Universität des Saarlandes

  公开号：EP2177510A1

  公开（公告）日：2010-04-21

  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.

  本发明提供了可异位调节 AGC 蛋白激酶和 Aurora 家族蛋白激酶活性或调节蛋白-蛋白相互作用的特异性小分子化合物、其生产方法、包含这些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性相关疾病的药物的用途。
• 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.