methyl 4-(benzyloxy)-3-methylbenzoate | 1439364-88-1

• 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: methyl 4-(benzyloxy)-3-methylbenzoate
• 英文别名: methyl 3-methyl-4-phenylmethoxybenzoate
• CAS: 1439364-88-1
• 化学式: C₁₆H₁₆O₃
• 分子量: 256.301
• InChiKey: OUBGESSJRCZNMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  methyl 4-(benzyloxy)-3-methylbenzoate 在 palladium on activated charcoal 、 三氟化硼乙醚 、 水 、 甲酸铵 、 sodium hydride 、 potassium carbonate 、 potassium iodide 、 potassium hydroxide 作用下， 以 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 22.5h， 生成 5-(3-(4-(3,3-dimethyl-2-oxobutoxy)-3-methylphenyl)pentan-3-yl)-1-methylpyrrole-2-carboxylic acid
  参考文献：
  名称：

  Novel nonsecosteroidal VDR agonists with phenyl-pyrrolyl pentane skeleton

  摘要：

  In order to find the vitamin D receptor (VDR) ligand whose VDR agonistic activity is separated from the calcemic activity sufficiently, novel nonsecosteroidal analogs with phenyl pyrrolyl pentane skeleton were synthesized and evaluated for the VDR binding affinity, antiproliferative activity in vitro and serum calcium raising ability in vivo (tacalcitol used as control). Among them, several compounds showed varying degrees of VDR agonistic and growth inhibition activities of the tested cell lines. The most effective compound 2g (EC50: 1.06 nM) exhibited stronger VDR agonistic activity than tacalcitol (EC50: 7.05 nM), inhibited the proliferations of HaCaT and MCF-7 cells with IC50 of 2.06 mu M and 0.307 mu M (tacalcitol: 2.07 mu M and 0.057 mu M) and showed no significant effect on serum calcium. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.015
• 作为产物：
  描述：

  4-羟基-3-甲基苯甲酸 在 硫酸 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 12.5h， 生成 methyl 4-(benzyloxy)-3-methylbenzoate
  参考文献：
  名称：

  Discovery of novel nonsteroidal VDR agonists with novel diarylmethane skeleton for the treatment of breast cancer

  摘要：

  Vitamin D receptor (VDR) is recognized as a potential target for the treatment of breast cancer which is the most common malignancy among women in the world. In this study, a series of nonsecosteroidal VDR agonists with a novel diarylmethane skeleton was designed, synthesized and the anti-tumor activities of these compounds were determined. Compound 28 was identified as the most effective agents in reducing the viability of MCF-7 cells, with a low IC50 via the inhibition of cell cycle and induction of apoptosis by regulating the expression of p21, Bcl2 and Bax. In addition, compound 28 showed high VDR-binding affinity and displayed significant VDR-agonistic activities. Further investigation revealed that compound 28 inhibited tumor growth in an orthotopic breast-tumor model without causing hypercalcemia which is the main side effect of secosteroidal VDR modulators. In summary, these findings discovered novel VDR modulators as promising candidates for cancer chemotherapy. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.024

文献信息

• [EN] HETEROCYCLIC INHIBITORS OF PCSK9<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES DE PCSK9
  申请人：CARDIO THERAPEUTICS PTY LTD

  公开号：WO2018165718A1

  公开（公告）日：2018-09-20

  This application relates to chemical compounds which may act as inhibitors of, or which may otherwise modulate the activity of, PCSK9, or a pharmaceutically acceptable salt, solvate, prodrug or polymorph thereof, and to compositions and formulations comprising such compounds, and methods of using and making such compounds. Compounds include compounds of Formula (I): (I) wherein A, D and Q are described herein.

  这种应用涉及可能作为PCSK9的抑制剂或以其他方式调节PCSK9活性的化合物，或其药用可接受的盐、溶剂化合物、前药或多型体，以及包含这些化合物的组合物和配方，以及使用和制备这些化合物的方法。化合物包括式(I)的化合物：(I)其中A、D和Q如本文所述。
• Nickel and Nucleophilic Cobalt-Catalyzed Trideuteriomethylation of Aryl Halides Using Trideuteriomethyl <i>p</i>-Toluenesulfonate
  作者：Kimihiro Komeyama、Yuta Yamahata、Itaru Osaka

  DOI：10.1021/acs.orglett.8b01863

  日期：2018.7.20

  Herein, a novel approach for the trideuteriomethylation of aryl halides using nickel and nucleophilic cobalt catalysts and the readily available trideuteriomethyl p-toluenesulfonate (CD3OTs) is described. This method provides access to a wide range of CD3-containing arenes. Moreover, a transmethylation step is revealed as crucial in the nickel/cobalt catalytic mechanism.

  在此，描述了一种使用镍和亲核钴催化剂以及易于获得的对甲苯磺酸三氘甲基甲基酯（CD 3 OT）对芳基卤化物进行三氘甲基甲基化的新方法。该方法提供了进入范围广泛的含CD 3的芳烃的途径。此外，揭示了甲基转移步骤对于镍/钴催化机理至关重要。
• Identification of a Dual Autophagy and REV-ERB Inhibitor with <i>in Vivo</i> Anticancer Efficacy
  作者：Martina Palomba、Donatella Vecchio、Giulia Allavena、Vito Capaccio、Claudia De Mei、Rita Scarpelli、Benedetto Grimaldi

  DOI：10.1021/acs.jmedchem.3c01432

  日期：2024.1.11

  autophagy process appears as a promising target for anticancer interventions. Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) are the only FDA-approved autophagy flux inhibitors. Although diverse anticancer clinical trials are providing encouraging results, several limitations associated with the need of high dosage and long-term administration of these autophagy inhibitors are also emerging

  自噬过程似乎是抗癌干预的一个有希望的目标。氯喹 (CQ) 及其衍生物羟氯喹 (HCQ) 是 FDA 唯一批准的自噬通量抑制剂。尽管各种抗癌临床试验提供了令人鼓舞的结果，但也出现了与这些自噬抑制剂需要高剂量和长期给药相关的一些限制。我们发现，抑制 REV-ERB（一种调节昼夜节律和代谢的核受体）可增强 CQ 介导的癌细胞死亡，并鉴定出一类自噬和 REV-ERB 双重抑制剂，对多种肿瘤细胞显示出体外抗癌活性高于CQ。在此，我们描述了我们的先导优化策略，该策略导致化合物24被鉴定为双重自噬和 REV-ERB 抑制剂，显示出在阻断自噬方面的改进效力、增强的对癌细胞的毒性、最佳的药物样特性以及在小鼠中的功效作为单一抗癌剂的黑色素瘤异种移植模型。
• Heterocyclic inhibitors of PCSK9
  申请人：CARDIO THERAPEUTICS PTY LTD

  公开号：US11091466B2

  公开（公告）日：2021-08-17

  This application relates to chemical compounds which may act as inhibitors of, or which may otherwise modulate the activity of, PCSK9, or a pharmaceutically acceptable salt, solvate, prodrug or polymorph thereof, and to compositions and formulations comprising such compounds, and methods of using and making such compounds. Compounds include comprising of Formula (I): (I) wherein A, D and Q are described herein.

  本申请涉及可作为 PCSK9 抑制剂或以其他方式调节 PCSK9 活性的化合物，或其药学上可接受的盐、溶液剂、原药或多晶型物，还涉及包含此类化合物的组合物和制剂，以及使用和制造此类化合物的方法。化合物包括式（I）：(I) 其中 A、D 和 Q 如本文所述。
• Further Developments of the Phenyl-Pyrrolyl Pentane Series of Nonsteroidal Vitamin D Receptor Modulators as Anticancer Agents
  作者：Meixi Hao、Siyuan Hou、Lingjing Xue、Haoliang Yuan、Lulu Zhu、Cong Wang、Bin Wang、Chunming Tang、Can Zhang

  DOI：10.1021/acs.jmedchem.8b00106

  日期：2018.4.12

  The vitamin D (3) receptor (VDR), which belongs to the nuclear-receptor superfamily, is a potential molecular target for anticancer-drug discovery. In this study, a series of nonsteroidal vitamin D mimics with phenyl-pyrrolyl pentane skeletons with therapeutic potentials in cancer treatment were synthesized. Among them, 11b and 11g were identified as the most effective agents in reducing the viability of four cancer-cell lines, particularly those of breast-cancer cells, with IC50 values in the submicromolar-concentration range. In addition, 11b and 11g possessed VDR-binding affinities and displayed significant partial VDR-agonistic activities determined by dual-luciferase-reporter assays and human-leukemia-cell-line (HL-60)-differentiation assays. Furthermore, 11b and 11g inhibited tumor growth in an orthotopic breast-tumor model via inhibition of cell proliferation and induction of cell apoptosis. More importantly, 11b and 11g exhibited favorable pharmacokinetic behavior in vivo and did not increase serum calcium levels or cause any other apparent side effects. In summary, 11b and 11g act as novel VDR modulators and may be promising candidates for cancer chemotherapy.