3-benzoyl-5,6-benzo-3,4-dihydrocoumarin | 14103-22-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 高异黄酮
• 英文名称: 3-benzoyl-5,6-benzo-3,4-dihydrocoumarin
• 英文别名: 3-Benzoyl-5,6-benzo-3,4-dihydro-cumarin；2-benzoyl-1,2-dihydrobenzo[f]chromen-3-one；2-benzoyl-1H-benzo[f]chromen-3(2H)-one
• CAS: 14103-22-1
• 化学式: C₂₀H₁₄O₃
• 分子量: 302.329
• InChiKey: ZSSLJXUNDUZGRR-UHFFFAOYSA-N

物化性质

• 熔点：
  160-162 °C(Solv: ethanol (64-17-5))
• 沸点：
  520.3±39.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 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：

  3-benzoyl-5,6-benzo-3,4-dihydrocoumarin 在 肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以100 mg的产率得到4-[(2-hydroxynaphthalen-1-yl)methyl]-5-phenyl-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：

  3-苯甲酰苯并[f]香豆素 在 吡啶 、 sodium tetrahydroborate 作用下， 反应 5.0h， 以50%的产率得到3-benzoyl-5,6-benzo-3,4-dihydrocoumarin
  参考文献：
  名称：

  氧化脱羧次碘酸铵催化二氢苯并呋喃合成

  摘要：

  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。

  DOI：

  10.1039/d2ob00463a

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。
• Methods for inhibiting deacetylase activity
  申请人：Bedaloy Antonio

  公开号：US20050079995A1

  公开（公告）日：2005-04-14

  A method for identifying a compound that inhibits the NAD + -dependent deacetylase activity of a SIR2 protein is disclosed. These compounds are useful for the treatment of cancers and other diseases, through the activation of silenced genes, through the promotion of apoptosis in cancerous cells, and through the inhibition of transcriptional repressor activity in oncogenes.

  揭示了一种用于识别抑制SIR2蛋白的NAD+-依赖性去乙酰化酶活性的化合物的方法。这些化合物通过激活沉默基因、促进癌细胞凋亡以及抑制癌基因转录抑制因子活性，对治疗癌症和其他疾病有用。
• [EN] COMPOSITIONS AND METHODS FOR INHIBITING N-SMASE2<br/>[FR] COMPOSITIONS ET PROCÉDÉS D'INHIBITION DE LA N-SMASE2
  申请人：UNIV CALIFORNIA

  公开号：WO2019055832A1

  公开（公告）日：2019-03-21

  Provided herein are compounds of Formula (I) and (II) and their salts, and compositions comprising such compounds that are useful for useful for modulating neutral sphingomyelinase 2 (n-SMase2) in cells. Also disclosed herein are methods of using the disclosed compounds and compositions for inhibiting the spread of Tau seeds from donor cells to recipient cells. Moreover, disclosed herein are methods of using the disclosed compounds and compositions for treating or preventing a neurodegenerative disorder, such as a tauopathy, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis (ALS).

  本文提供了化合物I和II及其盐，以及包含这些化合物的组合物，用于调节细胞中的中性鞘磷脂酰胆碱酰肌醇酶2（n-SMase2）。本文还披露了使用上述化合物和组合物抑制Tau种子从供体细胞传播到受体细胞的方法。此外，本文还披露了使用上述化合物和组合物治疗或预防神经退行性疾病的方法，例如tau病理、阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）、Lewy体痴呆、额颞叶痴呆和肌萎缩侧索硬化症（ALS）。
• Selective Reduction of the Endocyclic Double Bond of 3-Substituted Coumarins­ by Hantzsch 1,4-Dihydropyridine
  作者：Li Yang、Wei Yu、Zhengang Liu、Qiang Liu、Wei Zhang、Ruizhu Mu、Zhong-Li Liu

  DOI：10.1055/s-2006-926317

  日期：——

  Hantzsch 1,4-dihydropyridine is a valuable reagent to effect the chemoselective reduction of the 3,4-double bond of 3-substituted coumarins.

  汉茨1,4-二氢吡啶是一种用于对3-取代香豆素的3,4-双键进行化学选择性还原的宝贵试剂。
• 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.