2-(4-bromobenzoyl)-3H-benzo[f ]chromen-3-one | 113722-05-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 2-(4-bromobenzoyl)-3H-benzo[f ]chromen-3-one
• 英文别名: 2-(4-Bromobenzoyl)benzo[f]chromen-3-one
• CAS: 113722-05-7
• 化学式: C₂₀H₁₁BrO₃
• 分子量: 379.21
• InChiKey: MEALQBBPURKJQB-UHFFFAOYSA-N

物化性质

• 熔点：
  245-248 °C
• 沸点：
  582.8±50.0 °C(Predicted)
• 密度：
  1.564±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  2-(4-bromobenzoyl)-3H-benzo[f ]chromen-3-one 在 吡啶 、 sodium tetrahydroborate 、 肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 5-(4-bromophenyl)-4-[(2-hydroxynaphthalen-1-yl)methyl]-2,3-dihydro-1H-pyrazol-3-one
  参考文献：
  名称：

  Development of Pyrazolone and Isoxazol-5-one Cambinol Analogues as Sirtuin Inhibitors

  摘要：

  Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging in eukaryotic cells. In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 approximate to 50 mu M for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity. In the current study, we used saturation transfer difference (STD) NMR experiments with recombinant SIRT1 and 20 to map parts of the inhibitor that interacted with the protein. Our ongoing efforts to optimize cambinol analogues for potency and selectivity have resulted in the identification of isoform selective analogues: 17 with >7.8-fold selectivity for SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively. In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class. may be predominantly due to SIRT2 inhibition.

  DOI：

  10.1021/jm4018064
• 作为产物：
  描述：

  2-萘酚 在 哌啶 、 四氯化钛 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 2-(4-bromobenzoyl)-3H-benzo[f ]chromen-3-one
  参考文献：
  名称：

  Development of Pyrazolone and Isoxazol-5-one Cambinol Analogues as Sirtuin Inhibitors

  摘要：

  Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging in eukaryotic cells. In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 approximate to 50 mu M for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity. In the current study, we used saturation transfer difference (STD) NMR experiments with recombinant SIRT1 and 20 to map parts of the inhibitor that interacted with the protein. Our ongoing efforts to optimize cambinol analogues for potency and selectivity have resulted in the identification of isoform selective analogues: 17 with >7.8-fold selectivity for SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively. In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class. may be predominantly due to SIRT2 inhibition.

  DOI：

  10.1021/jm4018064

文献信息

• [EN] PYRIMIDE DERIVATIVES AND THEIR PHARMACEUTICAL USE<br/>[FR] DÉRIVÉS DE PYRIMIDE ET LEUR USAGE PHARMACEUTIQUE
  申请人：UNIV DUNDEE

  公开号：WO2010038043A1

  公开（公告）日：2010-04-08

  The invention provides a compound according to formula (I): wherein: X is O or S; Y is O or S; each Ar and Ar' is independently a mono-, bi- or tricyclic aryl or heteroaryl group optionally substituted with one or more substituents selected from halo, alkyl, aryl, heteroaryl, hydroxyl, nitro, amino, alkoxy, alkylthio, cyano, thio, ester, acyl and amido; each R2 is independently hydrogen, halo, alkyl, aryl, heteroaryl, hydroxyl, nitro, amino, alkoxy, alkylthio, cyano and thio; and R1 is as defined herein, or a physiologically acceptable salt, solvate, ester, amide or other physiologically functional derivative thereof.

  该发明提供了一个符合以下式（I）的化合物：其中：X为O或S；Y为O或S；每个Ar和Ar'独立地是一个单环、双环或三环芳基或杂芳基，可选地取代一个或多个卤素、烷基、芳基、杂芳基、羟基、硝基、氨基、烷氧基、烷硫基、氰基、硫基、酯基、酰基和酰胺基；每个R2独立地是氢、卤素、烷基、芳基、杂芳基、羟基、硝基、氨基、烷氧基、烷硫基、氰基和硫基；R1如本文所定义，或其生理上可接受的盐、溶剂合物、酯、酰胺或其他生理功能衍生物。
• Regioselective Coupling Reactions of Coumarins with Aldehydes or Di-<i>tert</i>-butyl Peroxide (DTBP) through a C(sp²)-H Functionalization Process
  作者：Wannian Zhao、Lei Xu、Yingcai Ding、Ben Niu、Ping Xie、Zhaogang Bian、Denghong Zhang、Aihua Zhou

  DOI：10.1002/ejoc.201501251

  日期：2016.1

  have developed two new coupling reactions that involve coumarins and either aldehydes or di-tert-butyl peroxide (DTBP) in the presence of inexpensive copper or iron catalysts. Both of these reactions proceed through a C(sp2)–H functionalization process to regioselectivity generate keto- or methyl-substituted coumarin derivatives in moderate to good yields These coupling reactions will enrich current coumarin

  香豆素衍生物是药物发现中非常有价值的化合物。在此，我们开发了两种新的偶联反应，它们涉及香豆素和醛或二叔丁基过氧化物 (DTBP) 在廉价的铜或铁催化剂存在下。这两个反应都通过 C(sp2)-H 官能化过程进行，以区域选择性生成酮或甲基取代的香豆素衍生物，产率中等至良好。这些偶联反应将丰富当前的香豆素化学。
• Oxidative decarboxylative ammonium hypoiodite-catalysed dihydrobenzofuran synthesis
  作者：Katharina Röser、Anna Scheucher、Christopher Mairhofer、Matthias Bechmann、Mario Waser

  DOI：10.1039/d2ob00463a

  日期：——

  The catalytic use of quaternary ammonium iodides under oxidative conditions allows for the direct conversion of readily available β-ketolactones into dihydrobenzofurans via a decarboxylative oxidative cycloetherification sequence facilitated by an in situ formed ammonium hypoiodite species.

  在氧化条件下催化使用季铵碘化物可以通过原位形成的次碘酸铵物质促进的脱羧氧化环醚化序列将容易获得的 β-酮内酯直接转化为二氢苯并呋喃。
• Novel Cambinol Analogs as Sirtuin Inhibitors: Synthesis, Biological Evaluation, and Rationalization of Activity
  作者：Federico Medda、Rupert J. M. Russell、Maureen Higgins、Anna R. McCarthy、Johanna Campbell、Alexandra M. Z. Slawin、David P. Lane、Sonia Lain、Nicholas J. Westwood

  DOI：10.1021/jm8014298

  日期：2009.5.14

  The tenovins and cambinol are two classes of sirtuin inhibitor that exhibit antitumor activity in preclinical models. This report describes modifications to the core structure of cambinol, in particular by incorporation of substitutents at the N1-position, which lead to increased potency and modified selectivity. These improvements have been rationalized using molecular modeling techniques. The expected functional selectivity in cells was also observed for both a SIRT1 and a SIRT2 selective analog.
• Synthesis of functionalized benzo[f]2H-chromenes and evaluation of their antimicrobial activities
  作者：Irom Harimala Chanu、Laishram Ronibala Devi、Nonibala Khumanthem、N. Irabanta Singh、Dalip Kumar、Okram Mukherjee Singh

  DOI：10.1134/s1068162017020054

  日期：2017.3

  Knoevenagel cyclocondensations of alpha-hydroxy naphthaldehyde with beta-oxodithioesters and ketene dithioacetals yielded 2H-benzo[f]chromene-2-thiones and 2H-benzo[f]chromen-2-ones, respectively, in high yields. The newly synthesized compounds were evaluated for antifungal and antibacterial activities. Among them, compounds (2-furyl)(3-thioxo-3H-benzo[f]chromen-2-yl)methanone and phenyl(3-oxo-3H-benzo[f]chromen-2-yl)methanone exhibited excellent antifungal activity against tested fungi Curvularia lunata and Fusarium moniliforme. The highest antibacterial activity against the tested bacteria Escherichia coli and Staphylococcus aureus was observed for (4-chlorophenyl)(3-oxo-3H-benzo[f]chromen-2-yl)methanone. The results of antimicrobial screening demonstrate that (2-furyl)(3-thioxo-3H-benzo[f]chromen-2-yl)methanone, phenyl(3-oxo-3H-benzo[f]chromen-2-yl)methanone, and (4-chlorophenyl)(3-oxo-3H-benzo[f]chromen-2-yl)methanone are promising as antimicrobial drugs.