2-(2'-chlorobenzoyl)-3H-benzo[f]chromen-3-one | 1148118-68-6

• 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-(2'-chlorobenzoyl)-3H-benzo[f]chromen-3-one
• 英文别名: 2-(2-chlorobenzoyl)-3H-benzo[f]chromen-3-one；2-(2-Chlorobenzoyl)benzo[f]chromen-3-one
• CAS: 1148118-68-6
• 化学式: C₂₀H₁₁ClO₃
• 分子量: 334.759
• InChiKey: MDEVRBYVESNZPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 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-(2'-chlorobenzoyl)-3H-benzo[f]chromen-3-one 在 吡啶 、 sodium tetrahydroborate 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 6-(2-chlorophenyl)-5-[(2-hydroxynaphthalen-1-yl)methyl]-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
  参考文献：
  名称：

  Simplification of the tetracyclic SIRT1-selective inhibitor MC2141: Coumarin- and pyrimidine-based SIRT1/2 inhibitors with different selectivity profile

  摘要：

  In this report we describe the synthesis and biological characterization of two series of sirtuins' inhibitors (SIRTi), designed as simplification products of the previously reported SIRT1-selective inhibitor MC2141 (4). In the first series (5a-t) we report a number of 2-substituted-1,2-dihydrobenzo[f] chromen-3-ones with a marked selectivity for the inhibition of SIRT2 over SIRT1. Some of such derivatives showed also high pro-apoptotic (5i and 5l) and/or cytodifferentiating (5d, 5i, and 5o) properties in a human leukemia cell line (U937). The second group of SIRTi (6a-q) is characterized by some analogues of cambinol (3), a well known SIRTi active against the Burkitt lymphoma. Such compounds, differently from the unselective prototype, are endowed with a selective inhibition of SIRT1 over SIRT2, and, in some cases (6j, 6k, and 6q), are more efficient than 3 to induce apoptosis in U937 cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.025
• 作为产物：
  描述：

  2-羟基-1-萘甲醛 、 (2-氯苯甲酰)乙酸乙酯 在 哌啶 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以89%的产率得到2-(2'-chlorobenzoyl)-3H-benzo[f]chromen-3-one
  参考文献：
  名称：

  Characterization of Sirtuin Inhibitors in Nematodes Expressing a Muscular Dystrophy Protein Reveals Muscle Cell and Behavioral Protection by Specific Sirtinol Analogues

  摘要：

  In oculopharyngeal muscular dystrophy (OPMD), a disease caused by polyalanine expansion in the nuclear protein PABPN1, the genetic inhibition or sirtuins and treatment with sirtuin inhibitors protect from mutant PABPN1 toxicity in transgenic nematodes. Here, we tested the SIRT1/2 inhibitors 1-12, bearing different degrees of inhibition, for protection against mutant PABPN1 toxicity in Caenorhabditis elegans. Compounds 2, 4, and 11 were the most efficient, revealing a potential therapeutic application for muscle cell protection in OPMD.

  DOI：

  10.1021/jm9013345

文献信息

• 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.
• Characterization of Sirtuin Inhibitors in Nematodes Expressing a Muscular Dystrophy Protein Reveals Muscle Cell and Behavioral Protection by Specific Sirtinol Analogues
  作者：Matthieu Y. Pasco、Dante Rotili、Lucia Altucci、Francesca Farina、Guy A. Rouleau、Antonello Mai、Christian Néri

  DOI：10.1021/jm9013345

  日期：2010.2.11

  In oculopharyngeal muscular dystrophy (OPMD), a disease caused by polyalanine expansion in the nuclear protein PABPN1, the genetic inhibition or sirtuins and treatment with sirtuin inhibitors protect from mutant PABPN1 toxicity in transgenic nematodes. Here, we tested the SIRT1/2 inhibitors 1-12, bearing different degrees of inhibition, for protection against mutant PABPN1 toxicity in Caenorhabditis elegans. Compounds 2, 4, and 11 were the most efficient, revealing a potential therapeutic application for muscle cell protection in OPMD.
• Simplification of the tetracyclic SIRT1-selective inhibitor MC2141: Coumarin- and pyrimidine-based SIRT1/2 inhibitors with different selectivity profile
  作者：Dante Rotili、Vincenzo Carafa、Domenico Tarantino、Giorgia Botta、Angela Nebbioso、Lucia Altucci、Antonello Mai

  DOI：10.1016/j.bmc.2011.01.025

  日期：2011.6

  In this report we describe the synthesis and biological characterization of two series of sirtuins' inhibitors (SIRTi), designed as simplification products of the previously reported SIRT1-selective inhibitor MC2141 (4). In the first series (5a-t) we report a number of 2-substituted-1,2-dihydrobenzo[f] chromen-3-ones with a marked selectivity for the inhibition of SIRT2 over SIRT1. Some of such derivatives showed also high pro-apoptotic (5i and 5l) and/or cytodifferentiating (5d, 5i, and 5o) properties in a human leukemia cell line (U937). The second group of SIRTi (6a-q) is characterized by some analogues of cambinol (3), a well known SIRTi active against the Burkitt lymphoma. Such compounds, differently from the unselective prototype, are endowed with a selective inhibition of SIRT1 over SIRT2, and, in some cases (6j, 6k, and 6q), are more efficient than 3 to induce apoptosis in U937 cells. (C) 2011 Elsevier Ltd. All rights reserved.