4-(氯甲基)-2H-苯并[h]苯并吡喃-2-酮 | 41321-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 中文名称: 4-(氯甲基)-2H-苯并[h]苯并吡喃-2-酮
• 英文名称: 4-(chloromethyl)-2H-benzo[h]chromen-2-one
• 英文别名: 4-(chloromethyl)benzo[h]chromen-2-one
• CAS: 41321-76-0
• 化学式: C₁₄H₉ClO₂
• 分子量: 244.677
• InChiKey: ZKKZXZILYDCFSC-UHFFFAOYSA-N

物化性质

• 熔点：
  166-169 °C(Solv: ethanol (64-17-5))
• 沸点：
  434.4±33.0 °C(Predicted)
• 密度：
  1.346±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 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：

  4-(氯甲基)-2H-苯并[h]苯并吡喃-2-酮 在 sodium carbonate 、 溶剂黄146 、 三乙胺 、 sodium iodide 、 三氯氧磷 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 5.0h， 生成 C₃₃H₃₁N₉O₂S
  参考文献：
  名称：

  Discovery of tofacitinib derivatives as orally active antitumor agents based on the scaffold hybridization strategy

  摘要：

  In this work, a novel series of tofacitinib analogs were designed and synthesized based on the scaffold hybridization strategy and then evaluated for their antiproliferative activity toward three gastric cancer cell lines, leading to the identification of compound C18 which exhibited potent inhibitory activity against MGC-803 cell lines with an IC50 value of 2.68 mu M. Compound C18 could effectively inhibit the colony formation, suppress the cell migration and induce apoptosis of MGC-803 cells through activating the p38 and JNK signaling pathways, while C18 showed no obvious effect on the cell cycle distribution in MGC-803 cells. In addition, C18 could initiate mitochondrial dysfunction of MGC-803 cells. Besides, in vivo antitumor studies indicated that C18 could inhibit gastric cancer tumor growth in vivo without obvious global toxicity. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112601
• 作为产物：
  描述：

  4-氯乙酰乙酸甲酯 、 萘酚 在 aluminum oxide 、 甲烷磺酸 作用下， 反应 0.58h， 以90%的产率得到4-(氯甲基)-2H-苯并[h]苯并吡喃-2-酮
  参考文献：
  名称：

  Al2O3/MeSO3H (AMA) as a novel heterogeneous system for synthesis of coumarins under mild conditions

  摘要：

  Al2O3/MeSO3H (AMA) is found to be an efficient reagent for the Pechman condensation reaction of phenols and beta- ketoesters under solvent free conditions. The reaction protocol is simple, cost- effective, solvent free and gives good isolated yield with high purity and good regioselectivity.

  DOI：

  10.1016/s0385-5414(07)81208-1

文献信息

• Synthesis of Furoneoflavones Modified by Coumarin and (HET)Aroyl Substituents
  作者：T. V. Shokol、V. S. Moskvina、Ye. K. Hlibov、M. S. Frasinyuk、V. P. Khilya

  DOI：10.1007/s10600-021-03275-4

  日期：2021.1

  Furo[3,2-g]neoflavones and furo[2,3-h]neoflavones modified by coumarin and (het)aroyl substituents were synthesized via reactions of 7-hydroxy-6(8)-acetyl(formyl)neoflavones with substituted phenacyl bromides, 2-bromacetylbenzofuran, and 4-chloromethylcoumarins.

  通过7-羟基-6(8)-乙酰(甲酰)新黄酮与取代苯乙酰溴、2-溴乙酰苯并呋喃和4-氯甲基香豆素的反应，合成了经香豆素和（杂）芳酰基修饰的呋喃[3,2-g]新黄酮和呋喃[2,3-h]新黄酮。
• Discovery of [1,2,4]triazolo[1,5-a]pyrimidine derivatives as new bromodomain-containing protein 4 (BRD4) inhibitors
  作者：Shuai Wang、Dandan Shen、Lijie Zhao、Xiaohan Yuan、Jialing Cheng、Bin Yu、Yichao Zheng、Hongmin Liu

  DOI：10.1016/j.cclet.2019.08.029

  日期：2020.2

  Abstract Targeting bromodomain-containing protein 4 (BRD4) has been proved to be an effective strategy for cancer therapy. To date, numerous BRD4 inhibitors and degraders have been identified, some of which have advanced into clinical trials. In this work, a focused library of new [1,2,4]triazolo[1,5-a]pyrimidine derivatives were discovered to be able to inhibit BRD4. WS-722 inactivated BRD4 (BD1/BD2)

  摘要靶向含溴结构域的蛋白质4（BRD4）已被证明是一种有效的癌症治疗策略。迄今为止，已鉴定出许多BRD4抑制剂和降解剂，其中一些已进入临床试验。在这项工作中，发现了新的[1,2,4]三唑并[1,5-a]嘧啶衍生物的聚焦文库能够抑制BRD4。WS-722使BRD4（BD1 / BD2），BRD2（BD1 / BD2）和BRD3（BD1 / BD2）广泛失活，IC50值小于5μmol/ L。此外，WS-722抑制THP-1细胞的生长，IC50值为3.86μmol/ L。像（+）-JQ1一样，WS-722以可逆方式抑制BRD4，并增强了蛋白质稳定性。对接研究表明，WS-722占据了中央乙酰赖氨酸（Kac）的结合腔，并与Asn140形成了氢键。在THP-1细胞中，WS-722显示出对BRD4的靶标参与。还检查了WS-722对THP-1细胞的细胞作用，表明WS-722可以阻断c-MYC表达，诱导G0
• Development of Highly Potent, Selective, and Cellular Active Triazolo[1,5-<i>a</i>]pyrimidine-Based Inhibitors Targeting the DCN1–UBC12 Protein–Protein Interaction
  作者：Shuai Wang、Lijie Zhao、Xiao-Jing Shi、Lina Ding、Linlin Yang、Zhi-Zheng Wang、Dandan Shen、Kai Tang、Xiao-Jing Li、MAA Mamun、Huiju Li、Bin Yu、Yi-Chao Zheng、Shaomeng Wang、Hong-Min Liu

  DOI：10.1021/acs.jmedchem.9b00113

  日期：2019.3.14

  the identification of new triazolo[1,5- a]pyrimidine-based inhibitors targeting the DCN1-UBC12 interaction. Compound WS-383 blocks the DCN1-UBC12 interaction (IC50 = 11 nM) reversibly and shows selectivity over selected kinases. WS-383 exhibits cellular target engagement to DCN1 in MGC-803 cells. WS-383 inhibits Cul3/1 neddylation selectively over other cullins and also induces accumulation of p21, p27

  cullin-ring泛素连接酶（CRL）负责约20％的细胞蛋白质降解并调节多种细胞过程，并且CRL的功能障碍与人类疾病有关。瞄准CRL已成为治疗人类疾病的新兴策略。在本文中，我们描述了从我们的内部库中发现一种命中化合物的信息以及基于结构的进一步优化，这使得能够鉴定靶向DCN1-UBC12相互作用的新的基于三唑并[1,5- a]嘧啶的抑制剂。化合物WS-383可逆地阻止DCN1-UBC12相互作用（IC50 = 11 nM），并显示出对所选激酶的选择性。WS-383在MGC-803细胞中表现出对DCN1的细胞靶标接合。WS-383选择性抑制Cul3 / 1的二烯化作用高于其他cullins，并且还诱导p21，p27和NRF2的积累。
• Synthesis of the Coumarins via Pechmann Method in the Presence of Environmentally Friendly Y(NO₃)₃×6H₂O
  作者：Bahador Karami、Mahtab Kiani

  DOI：10.1002/jccs.201200610

  日期：2014.2

  Several substituted coumarins can be prepared in high yield and purity by direct reaction of β‐keto esters and phenol derivatives in the presence of a catalytic amount Y(NO3)3×6H2O as Lewis acid and at ambient temperature under solvent‐free conditions.

  通过在催化量的Y（NO 3）3 ×6H 2 O（路易斯酸）存在下，在室温和无溶剂条件下，通过β-酮酸酯和苯酚衍生物的直接反应，可以高收率和高纯度地制备几种取代的香豆素。条件。
• Nanosilica molybdic acid: synthesis, characterization and application as a green and reusable catalyst for the Pechmann condensation
  作者：Mahtab Kiani、Bahador Karami

  DOI：10.1007/s13738-016-1016-6

  日期：2017.3

  AbstractNanosilica molybdic acid (SMA NPs) was founded as an efficient and recyclable nanocatalyst for the synthesis of coumarin derivatives in excellent yields with good purity. Nano-SMA as a new solid acid was characterized by X-ray fluorescence, X-ray diffraction, energy-dispersive X-ray analyzer, transmission electron microscopy and Fourier transform infrared spectroscopy. Coumarin derivatives

  摘要纳米二氧化硅钼酸（SMA NPs）是一种高效，可回收的纳米催化剂，用于以良好的收率和良好的纯度合成香豆素衍生物。纳米SMA是一种新型的固体酸，其特征在于X射线荧光，X射线衍射，能量色散X射线分析仪，透射电子显微镜和傅立叶变换红外光谱。香豆素衍生物是通过在无溶剂条件下于80°C下苯酚和β-酮酸酯的Pechmann缩合反应获得的。本方法的主要优点是高产率，较短的反应时间和绿色化学方法，后处理简单且催化剂便宜且可重复使用。 图形概要