4-([1,1'-biphenyl]-4-ylmethoxy)benzaldehyde | 1221413-93-9

• 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: 4-([1,1'-biphenyl]-4-ylmethoxy)benzaldehyde
• 英文别名: 4-[(4-phenylphenyl)methoxy]benzaldehyde；4-(biphenyl-4-ylmethoxy)benzaldehyde
• CAS: 1221413-93-9
• 化学式: C₂₀H₁₆O₂
• 分子量: 288.346
• InChiKey: WSEFTLHQOSPACN-UHFFFAOYSA-N

物化性质

• 沸点：
  476.0±33.0 °C(predicted)
• 密度：
  1.148±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,4-噻唑烷二酮 、 4-([1,1'-biphenyl]-4-ylmethoxy)benzaldehyde 在 哌啶 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以83.6%的产率得到5-(4-(biphenyl-4-ylmethoxy)benzylidene)thiazolidine-2,4-dione
  参考文献：
  名称：

  Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors

  摘要：

  Prostaglandins have a short life in vivo because they are metabolized rapidly by oxidation to 15-ketoprostaglandins catalyzed by a cytosolic enzyme known as NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, CT-8, a thiazolidinedione analogue, was found to be a potent inhibitor of 15-PGDH. Structure-activity analysis indicated that the N-methylation of thiazolidine-2,4-dione, CT-8, abolished the inhibitory activity, whereas the introduction of an ethyl hydroxyl group at amine in CT-8 still had a good inhibitory effect. Based on the structures of the thiazolidinediones analogues and inhibitory activity, a range of benzylidene thiazolidinedione derivatives were synthesized with different substituents on the phenyl ring and their inhibitory activity was evaluated. Replacement of the cyclohexylethyl group of CT-8 with the hetero five-member ring increased the inhibitory potency. However, replacement of the cyclohexylethyl group with a hetero six-member ring decreased the inhibitory potency significantly. It was found that compound 2 (5-(4-(2-(thiophen-2yl) ethoxy) benzylidene) thiazolidine-2,4-dione) was the most potent inhibitor that was effective in the nanomolar range. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.016
• 作为产物：
  描述：

  联苯-4-甲醇 、 对羟基苯甲醛 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 4-([1,1'-biphenyl]-4-ylmethoxy)benzaldehyde
  参考文献：
  名称：

  Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors

  摘要：

  Prostaglandins have a short life in vivo because they are metabolized rapidly by oxidation to 15-ketoprostaglandins catalyzed by a cytosolic enzyme known as NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, CT-8, a thiazolidinedione analogue, was found to be a potent inhibitor of 15-PGDH. Structure-activity analysis indicated that the N-methylation of thiazolidine-2,4-dione, CT-8, abolished the inhibitory activity, whereas the introduction of an ethyl hydroxyl group at amine in CT-8 still had a good inhibitory effect. Based on the structures of the thiazolidinediones analogues and inhibitory activity, a range of benzylidene thiazolidinedione derivatives were synthesized with different substituents on the phenyl ring and their inhibitory activity was evaluated. Replacement of the cyclohexylethyl group of CT-8 with the hetero five-member ring increased the inhibitory potency. However, replacement of the cyclohexylethyl group with a hetero six-member ring decreased the inhibitory potency significantly. It was found that compound 2 (5-(4-(2-(thiophen-2yl) ethoxy) benzylidene) thiazolidine-2,4-dione) was the most potent inhibitor that was effective in the nanomolar range. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.016

文献信息

• Disruptor of telomeric silencing 1-like (DOT1L): disclosing a new class of non-nucleoside inhibitors by means of ligand-based and structure-based approaches
  作者：Manuela Sabatino、Dante Rotili、Alexandros Patsilinakos、Mariantonietta Forgione、Daniela Tomaselli、Fréderic Alby、Paola B. Arimondo、Antonello Mai、Rino Ragno

  DOI：10.1007/s10822-018-0096-z

  日期：2018.3

  Chemical inhibition of chromatin-mediated signaling involved proteins is an established strategy to drive expression networks and alter disease progression. Protein methyltransferases are among the most studied proteins in epigenetics and, in particular, disruptor of telomeric silencing 1-like (DOT1L) lysine methyltransferase plays a key role in MLL-rearranged acute leukemia Selective inhibition of DOT1L is an established attractive strategy to breakdown aberrant H3K79 methylation and thus overexpression of leukemia genes, and leukemogenesis. Although numerous DOT1L inhibitors have been several structural data published no pronounced computational efforts have been yet reported. In these studies a first tentative of multi-stage and LB/SB combined approach is reported in order to maximize the use of available data. Using co-crystallized ligand/DOT1L complexes, predictive 3-D QSAR and COMBINE models were built through a python implementation of previously reported methodologies. The models, validated by either modeled or experimental external test sets, proved to have good predictive abilities. The application of these models to an internal library led to the selection of two unreported compounds that were found able to inhibit DOT1L at micromolar level. To the best of our knowledge this is the first report of quantitative LB and SB DOT1L inhibitors models and their application to disclose new potential epigenetic modulators.

  通过化学抑制涉及染色质介导信号传导的蛋白质，已被确立为驱动表达网络和改变疾病进展的策略。蛋白质甲基转移酶是表观遗传学中研究最多的蛋白质之一，尤其是破坏端粒沉默1-样（DOT1L）赖氨酸甲基转移酶，在MLL重组的急性白血病中扮演关键角色。选择性抑制DOT1L是一种确立的有吸引力的策略，以打破异常的H3K79甲基化，从而抑制白血病基因的过度表达和白血病发生。尽管已经发表了多个DOT1L抑制剂的结构数据，但尚未报道显著的计算努力。在这些研究中，首次尝试了多阶段和LB/SB结合的方法，以最大限度地利用可用数据。利用共结晶的配体/DOT1L复合物，通过之前报道的方法的python实现，建立了预测性的3-D QSAR和COMBINE模型。这些模型，通过模型或实验的外部测试集验证，证明具有良好的预测能力。这些模型应用于内部库，导致选择两个未报告的化合物，发现它们能够在微摩尔水平抑制DOT1L。据我们所知，这是首次报道定量LB和SB DOT1L抑制剂模型及其应用于揭示新的潜在表观遗传调控因子。
• NOVEL THIAZOLIDINEDIONE DERIVATIVE AND USE THEREOF
  申请人：Cho Hoon

  公开号：US20110269954A1

  公开（公告）日：2011-11-03

  The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.

  本发明涉及由以下式（I）表示的新型噻唑烷二酮衍生物及其用途。更具体地说，本发明涉及由以下式（I）表示的新型噻唑烷二酮衍生物以及包含其的药物组合物。根据本发明的式（I）的新型噻唑烷二酮衍生物可以通过抑制分解前列腺素的15-羟基前列腺素脱氢酶（15-PGDH）的活性，有效用于预防或治疗心血管疾病、胃肠道疾病和肾脏疾病，同时也用于预防脱发和促进头发生长，以及促进骨生成和伤口愈合。
• Synthesis of Phenyl- and Pyridyl-substituted Benzyloxybenzaldehydes by Suzuki-Miyaura Coupling Reactions
  作者：Hedvig Bölcskei、Andrea Német-Hanzelik、Zsófia Dubrovay、Viktor Háda、György Keglevich

  DOI：10.2174/1570180816666181106123809

  日期：2019.10.23

  starting materials for the synthesis of biologically active compounds. Methods: Biaryl-methoxybenzaldehydes and pyridyl-aryl-methoxybenzaldehydes were synthesized by the Suzuki-Miyaura cross-coupling reactions as intermediates of potential drug substances. Three different catalytic approaches were compared. The classical Suzuki method utilising tetrakis(triphenylphosphine)palladium and sodium ethoxide, the

  背景：在各个位置取代的芳基-甲氧基苯甲醛可作为合成生物活性化合物的重要原料。 方法：通过Suzuki-Miyaura交叉偶联反应，将潜在的药物中间体作为中间体合成了联芳基-甲氧基苯甲醛和吡啶基-芳基-甲氧基苯甲醛。比较了三种不同的催化方法。研究了使用四（三苯基膦）钯和乙醇钠的经典Suzuki方法，使用乙酸钯和三（邻甲苯基）膦的方案以及使用四（三苯基膦）钯和碳酸铯的方法。 结果：选择的硼酸为经典的苯基硼酸，以及4-吡啶和3-吡啶硼酸。已合成了26种新的联芳基-甲氧基苯甲醛或吡啶基-苯基甲氧基苯甲醛，它们可能是药物活性化合物的中间体。 结论：Anderson等人的方法。首选，因为它在所有情况下都能提供令人满意的结果。
• Discovery of substituted benzyloxy-benzylamine inhibitors of acetyltransferase Eis and their anti-mycobacterial activity
  作者：Allan H. Pang、Keith D. Green、Nishad Thamban Chandrika、Atefeh Garzan、Ankita Punetha、Selina Y.L. Holbrook、Melisa J. Willby、James E. Posey、Oleg V. Tsodikov、Sylvie Garneau-Tsodikova

  DOI：10.1016/j.ejmech.2022.114698

  日期：2022.11

  yielded highly potent (IC50 ∼ 1 μM) Eis inhibitors, which did not inhibit other acetyltransferases. Crystal structures of Eis in complexes with three of the inhibitors showed that the inhibitors were bound in the aminoglycoside binding site of Eis, consistent with the competitive mode of inhibition, as established by kinetics measurements. When tested in Mtb cultures, two inhibitors (47 and 55) completely

  结核病对氨基糖苷类卡那霉素 (KAN) 耐药的一个临床重要机制是其乙酰化是由结核分枝杆菌( Mtb ) 乙酰转移酶 Eis 上调所催化的。在寻找 Eis 抑制剂的过程中，我们发现了一种具有取代的苄氧基-苄胺支架的抑制剂。对该结构家族中 38 种化合物的构效关系研究产生了高效 (IC 50 ∼ 1 μM) Eis 抑制剂，该抑制剂不抑制其他乙酰转移酶。Eis 与三种抑制剂复合物的晶体结构表明，抑制剂结合在 Eis 的氨基糖苷结合位点上，这与通过动力学测量建立的竞争性抑制模式一致。当在Mtb培养物中进行测试时，两种抑制剂（47和55）完全消除了高度 KAN 抗性菌株Mtb mc 2 6230 K204 对 KAN 的抗性，这可能是由于 Eis 抑制作为主要机制。即使在不存在 KAN 的情况下，其中 13 种化合物对Mtb和其他分枝杆菌也具有毒性，但对非分枝杆菌或哺乳动物细胞没有毒性。这种与 Eis
• QUINOLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES INHIBITING AUTOPHOSPHORYLATION OF GROWTH FACTOR RECEPTOR ORIGINATING IN PLATELET AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP0860433B1

  公开（公告）日：2002-07-03