(E)-3-(4-chlorophenyl)-1-(4-(methoxymethoxy)phenyl)prop-2-en-1-one | 1410102-52-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(4-chlorophenyl)-1-(4-(methoxymethoxy)phenyl)prop-2-en-1-one
• 英文别名: 3-(4-Chlorophenyl)-1-(4-methoxymethoxyphenyl)prop-2-en-1-one；(E)-3-(4-chlorophenyl)-1-[4-(methoxymethoxy)phenyl]prop-2-en-1-one
• CAS: 1410102-52-1
• 化学式: C₁₇H₁₅ClO₃
• 分子量: 302.757
• InChiKey: GZWNWQQNNPIPJR-NYYWCZLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-chlorophenyl)-1-(4-(methoxymethoxy)phenyl)prop-2-en-1-one 在 盐酸 、 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 8.0h， 生成 2-(1-(4-chlorophenyl)-3-(4-hydroxyphenyl)-3-oxopropyl)malonic acid
  参考文献：
  名称：

  2-(3-Oxo-1,3-diphenylpropyl)malonic Acids as Potent Allosteric Ligands of the PIF Pocket of Phosphoinositide-Dependent Kinase-1: Development and Prodrug Concept

  摘要：

  The protein kinase C-related kinase 2 (PRK2)interacting fragment (PIF) pocket of phosphoinositide-dependent kinase-1 (PDK1) was proposed as a novel target site for allosteric modulators. In the present work, We describe the design, synthesis, and structure-activity relationship of a series of 2-(3-oxo-1,3- diphenylprapyl)malonic acids as potent allosteric activators binding, to the PIF pocket: Some congeners displayed AC(50) values for PDK1 activation in the submicromolar range. The potency of the best compounds to stabilize PDK1 in a thermal stability shift assay was in the same order Of magnitude as that of the PIF pocket binding peptide PIFtide, suggesting comparable binding affinities to the pm pocket, The crystal structure of PDK1 in complex with compound 4h revealed that additional ionic interactions are mainly responsible for the increased potency compared to the monocarboxylate analogues. Notably, several compounds displayed high selectivity for PDK1 Employing a prodrug strategy, we were able to corrroborate the novel mechanism of action in cells.

  DOI：

  10.1021/jm3010477
• 作为产物：
  描述：

  对羟基苯乙酮 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 (E)-3-(4-chlorophenyl)-1-(4-(methoxymethoxy)phenyl)prop-2-en-1-one
  参考文献：
  名称：

  2-(3-Oxo-1,3-diphenylpropyl)malonic Acids as Potent Allosteric Ligands of the PIF Pocket of Phosphoinositide-Dependent Kinase-1: Development and Prodrug Concept

  摘要：

  The protein kinase C-related kinase 2 (PRK2)interacting fragment (PIF) pocket of phosphoinositide-dependent kinase-1 (PDK1) was proposed as a novel target site for allosteric modulators. In the present work, We describe the design, synthesis, and structure-activity relationship of a series of 2-(3-oxo-1,3- diphenylprapyl)malonic acids as potent allosteric activators binding, to the PIF pocket: Some congeners displayed AC(50) values for PDK1 activation in the submicromolar range. The potency of the best compounds to stabilize PDK1 in a thermal stability shift assay was in the same order Of magnitude as that of the PIF pocket binding peptide PIFtide, suggesting comparable binding affinities to the pm pocket, The crystal structure of PDK1 in complex with compound 4h revealed that additional ionic interactions are mainly responsible for the increased potency compared to the monocarboxylate analogues. Notably, several compounds displayed high selectivity for PDK1 Employing a prodrug strategy, we were able to corrroborate the novel mechanism of action in cells.

  DOI：

  10.1021/jm3010477

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。
• Highly efficient deprotection of phenolic tetrahydropyranyl and methoxymethyl ethers and sequel cyclization to indanones using Sn(IV)Cl4 catalyst
  作者：Naseem Ahmed、Gulab Khushalrao Pathe、B. Venkata Babu

  DOI：10.1016/j.tetlet.2014.05.009

  日期：2014.7

  Sn(IV)Cl4 catalyst provided a rapid and efficient deprotection method for the phenolic THP and MOM ethers and sequel intramolecular Friedel–Crafts alkylation reaction of THP and MOM protected chalcone epoxides under mild conditions. The reaction took 2–3 min to give the products in excellent yield (90–98%) at 0 °C without affecting the other functional groups.

  Sn（IV）Cl 4催化剂在温和条件下为酚THP和MOM醚以及THP和MOM保护的查耳酮环氧化物的后续分子内Friedel-Crafts烷基化反应提供了一种快速有效的脱保护方法。反应历时2-3分钟，在0°C时以优异的收率（90–98％）得到了产品，而没有影响其他官能团。
• β-Cyclodextrin in water: highly facile biomimetic one pot deprotection of phenolic THP/MOM/Ac/Ts ethers and concomitant regioselective cyclization of chalcone epoxides and 2′-aminochalcones
  作者：Sumit Kumar、Nishant Verma、Naseem Ahmed

  DOI：10.1039/c5ra15996b

  日期：——

  A mild and efficient one-pot deprotection of THP/MOM/Ac/Ts ethers and the concomitant cyclization of chalcone epoxides to 2-hydroxyindanones or 2′-aminochalcones to aza-flavanones using β-cyclodextrin in water has been developed. β-CD was found to be highly effective at carrying out the deprotection and sequential transformations in an eco-friendly environment affording moderate to excellent yields

  已经开发了在水中使用β-环糊精对THP / MOM / Ac / Ts醚进行温和有效的一锅脱保护以及将查尔酮环氧化物伴随环化为2-羟基茚满酮或2'-氨基查耳酮为氮杂黄酮的过程。发现β-CD在生态友好的环境中进行脱保护和顺序转化非常有效，在60°C下8-22分钟内可提供中等至极好的收率（59-99％）。在该反应中首次使用了水，这是一种生态友好的反应介质。所提出的方案的优点包括高产率和催化剂的可重复使用性，并且该方案排除了金属和有机溶剂的使用。与先前报道的方法相比，本方法温和得多，但更先进。
• A Green, Solvent-Free, Microwave-Assisted, High-Yielding YbCl₃Catalyzed Deprotection of THP/MOM/Ac/Ts Ethers of Chalcone Epoxide and 2′-Aminochalcone and Their Sequel Cyclization
  作者：Sumit Kumar、Nishant Verma、Iram Parveen、Naseem Ahmed

  DOI：10.1002/jhet.2517

  日期：2016.11

  Under microwave and solvent‐free conditions, YbCl3 efficiently catalyzed the deprotection of tetrahydropyran‐2‐yl, methoxymethyl (MOM), acetyl, and tosyl groups and sequel cyclization of chalcone epoxide to 2‐hydroxyindanone and 2′‐aminochalcone to aza‐flavanone. The reaction afforded the products in excellent yield (78–99%) at 850 W microwave heating within 1–5 min under eco‐friendly conditions. The

  在无微波和无溶剂的条件下，YbCl 3有效催化四氢吡喃-2-基，甲氧基甲基（MOM），乙酰基和甲苯磺酰基的脱保护作用，并将查尔酮环氧化物的续环化成2-羟基茚满酮和2'-氨基查尔酮成氮杂黄酮。 。该反应在环保条件下在1-5分钟内在850 W微波加热下以极好的收率（78–99％）提供了产品。所提出方案的优点包括高收率，使用微波辐射，无溶剂条件，催化剂可重用性以及无需通过柱色谱法纯化。本方法比先前报道的方法温和得多但先进得多。