7-O-p-chlorobenzyl umbelliferone | 305863-15-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 7-O-p-chlorobenzyl umbelliferone
• 英文别名: 7-(4-chlorobenzyloxy)coumarin；7-[(4-chlorophenyl)methoxy]-2H-chromen-2-one；7-[(4-chlorophenyl)methoxy]chromen-2-one
• CAS: 305863-15-4
• 化学式: C₁₆H₁₁ClO₃
• mdl: MFCD01553692
• 分子量: 286.715
• InChiKey: BAVJMUHAPDEZIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-chlorophenethyl)-2-cyanoacetamide 、 7-O-p-chlorobenzyl umbelliferone 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 5-amino-8-(4-chlorobenzyloxy)-3-(4-chlorophenethyl)-1H-chromeno[3,4-c]pyridine-2,4(3H,10bH)-dione
  参考文献：
  名称：

  Discovery of chromenes as inhibitors of macrophage migration inhibitory factor

  摘要：

  Macrophage migration inhibitory factor (MIF) is an essential signaling cytokine with a key role in the immune system. Binding of MIF to its molecular targets such as, among others, the cluster of differentiation 74 (CD74) receptor plays a key role in inflammatory diseases and cancer. Therefore, the identification of MIF binding compounds gained importance in drug discovery. In this study, we aim to discover novel MIF binding compounds by screening of a focused compound collection for inhibition of its tautomerase enzyme activity. Inspired by the known chromen-4-one inhibitor Orita-13, a focused collection of compounds with a chromene scaffold was screened for MIF binding. The library was synthesized using versatile cyanoacetamide chemistry to provide diversely substituted chromenes. The screening provided inhibitors with IC50's in the low micromolar range. Kinetic evaluation suggested that the inhibitors were reversible and did not bind in the binding pocket of the substrate. Thus, we discovered novel inhibitors of the MIF tautomerase activity, which may ultimately support the development of novel therapeutic agents against diseases in which MIF is involved. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.12.032
• 作为产物：
  描述：

  7-羟基香豆素 、 4-氯苄溴 在 potassium carbonate 作用下， 反应 12.0h， 生成 7-O-p-chlorobenzyl umbelliferone
  参考文献：
  名称：

  Synthesis and Biological Evaluation ofortho-ArylN-Hydroxycinnamides as Potent Histone Deacetylase (HDAC) 8 Isoform-Selective Inhibitors

  摘要：

  AbstractHistone deacetylases (HDACs) are a family of enzymes that play a crucial role in biological process and diseases. In contrast to other isozymes, HDAC8 is uniquely incapable of histone acetylation. In order to delineate its physiological function, we developed HDAC8‐selective inhibitors using knowledge‐based design combined with structural modeling techniques. Enzyme inhibitory analysis demonstrated that some of the resulting compounds (22 b, 22 d, 22 f, and 22 g) exhibited anti‐HDAC8 activity superior to PCI34051, a known HDAC8‐specific inhibitor, with IC50 values in the range of 5–50 nM. Among them, compound 22 d showed antiproliferative effects toward several human lung cancer cell lines (A549, H1299, and CL1‐5); it exhibited cytotoxicity against human lung CL1‐5 cells similar to that of SAHA yet without significant cytotoxicity for normal IMR‐90 cells. Expression profiling of HDAC isoforms in three cancer cell lines indicated that the HDAC8 level in CL1‐5 is higher than that in H1299 and CL1‐1 cells, a result consistent with the differential cytotoxicity of compound 22 d. These results suggest the effectiveness of our design concept, which may lead to a tool compound for studying the specific role of HDAC8 in cellular biological processes.

  DOI：

  10.1002/cmdc.201200300

文献信息

• HDAC8 inhibitors for treating cancer
  申请人：City of Hope

  公开号：US10308596B2

  公开（公告）日：2019-06-04

  Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.

  本文特别提供了通过抑制 HDAC8 治疗癌症的化合物和方法。
• Synthesis and Biological Evaluation of<i>ortho</i>-Aryl<i>N</i>-Hydroxycinnamides as Potent Histone Deacetylase (HDAC) 8 Isoform-Selective Inhibitors
  作者：Wei-Jan Huang、Yi-Ching Wang、Shi-Wei Chao、Chen-Yui Yang、Liang-Chieh Chen、Mei-Hsiang Lin、Wen-Chi Hou、Mei-Yu Chen、Tai-Lin Lee、Ping Yang、Chung-I Chang

  DOI：10.1002/cmdc.201200300

  日期：2012.10

  AbstractHistone deacetylases (HDACs) are a family of enzymes that play a crucial role in biological process and diseases. In contrast to other isozymes, HDAC8 is uniquely incapable of histone acetylation. In order to delineate its physiological function, we developed HDAC8‐selective inhibitors using knowledge‐based design combined with structural modeling techniques. Enzyme inhibitory analysis demonstrated that some of the resulting compounds (22 b, 22 d, 22 f, and 22 g) exhibited anti‐HDAC8 activity superior to PCI34051, a known HDAC8‐specific inhibitor, with IC50 values in the range of 5–50 nM. Among them, compound 22 d showed antiproliferative effects toward several human lung cancer cell lines (A549, H1299, and CL1‐5); it exhibited cytotoxicity against human lung CL1‐5 cells similar to that of SAHA yet without significant cytotoxicity for normal IMR‐90 cells. Expression profiling of HDAC isoforms in three cancer cell lines indicated that the HDAC8 level in CL1‐5 is higher than that in H1299 and CL1‐1 cells, a result consistent with the differential cytotoxicity of compound 22 d. These results suggest the effectiveness of our design concept, which may lead to a tool compound for studying the specific role of HDAC8 in cellular biological processes.
• HDAC8 INHIBITORS FOR TREATING CANCER
  申请人：City of Hope

  公开号：EP3035924A2

  公开（公告）日：2016-06-29
• [EN] HDAC8 INHIBITORS FOR TREATING CANCER<br/>[FR] INHIBITEURS DE L'HDAC8 POUR LE TRAITEMENT DU CANCER
  申请人：HOPE CITY

  公开号：WO2015026935A2

  公开（公告）日：2015-02-26

  Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.
• Yadav, Nisha; Auti, Prashant; George, Ginson, Journal of the Indian Chemical Society, 2020, vol. 97, # 8, p. 1265 - 1271
  作者：Yadav, Nisha、Auti, Prashant、George, Ginson、Paul, Atish T.

  DOI：——

  日期：——