2-(3'-bromobenzoyl)-3H-benzo[f]chromen-3-one | 1148118-35-7

• 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-(3'-bromobenzoyl)-3H-benzo[f]chromen-3-one
• 英文别名: 2-(3-bromobenzoyl)-3H-benzo[f ]chromen-3-one；2-(3-bromobenzoyl)-3H-benzo[f]chromen-3-one；2-(3-bromo-benzoyl)-benzo[f]chromen-3-one；2-(3-Bromobenzoyl)benzo[f]chromen-3-one
• CAS: 1148118-35-7
• 化学式: C₂₀H₁₁BrO₃
• 分子量: 379.21
• InChiKey: GROSRHVGIFUQIL-UHFFFAOYSA-N

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-(3'-bromobenzoyl)-3H-benzo[f]chromen-3-one 在 吡啶 、 sodium tetrahydroborate 作用下， 反应 3.0h， 以100%的产率得到2-(3-bromobenzoyl)-1H,2H-naphtho[2,1-b]pyran-3-one
  参考文献：
  名称：

  Discovery of Selective SIRT2 Inhibitors as Therapeutic Agents in B-Cell Lymphoma and Other Malignancies

  摘要：

  基因消融以及对SIRT2（一种NAD+依赖性蛋白去乙酰化酶）的药物抑制在各种癌症和神经退行性疾病中具有治疗效果。我们先前描述了一种双重SIRT1/SIRT2抑制剂称为cambinol（IC50分别为56和59微米），在体外对癌细胞显示细胞毒活性，并在Burkitt淋巴瘤小鼠异种移植模型中表现出明显的抗增殖效果。最近的一些研究表明，SIRT1和SIRT3在神经退行性和代谢性疾病以及某些癌症中具有保护作用，促使我们启动了一项药物化学工作，以开发基于cambinol的SIRT2特异性抑制剂，不具有SIRT1或SIRT3调节活性。在这里，我们描述了有效的基于cambinol的SIRT2抑制剂，其中几种显示出约600纳米的效力，对SIRT1和SIRT3的选择性分别为>300至>800倍。在体外，这些抑制剂对淋巴瘤和上皮癌细胞系具有毒性。特别是，化合物55（IC50 SIRT2 0.25微米，在50微米下对SIRT1和SIRT3的抑制<25%）和56（IC50 SIRT2 0.78微米，在50微米下对SIRT1和SIRT3的抑制<25%）显示出对B细胞淋巴瘤细胞具有凋亡以及强烈的抗增殖特性。

  DOI：

  10.3390/molecules25030455
• 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-(3'-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。
• 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.
• PYRIMIDE DERIVATIVES AND THEIR PHARMACEUTICAL USE
  申请人：The University Court of the University of Dundee

  公开号：EP2344462A1

  公开（公告）日：2011-07-20
• PYRIMIDINE DERIVATIVES AND THEIR PHARMACEUTICAL USE
  申请人：The University Court of the University of Dundee

  公开号：EP2344462B1

  公开（公告）日：2016-05-18
• Compounds
  申请人：Westwood Nicholas James

  公开号：US20110245282A1

  公开（公告）日：2011-10-06

  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 R 2 is independently hydrogen, halo, alkyl, aryl, heteroaryl, hydroxyl, nitro, amino, alkoxy, alkylthio, cyano and thio; and R 1 is as defined herein, or a physiologically acceptable salt, solvate, ester, amide or other physiologically functional derivative thereof.