5-(biphenyl-4-yl)-pentanoic acid N-hydroxyamide | 191228-43-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(biphenyl-4-yl)-pentanoic acid N-hydroxyamide
• 英文别名: N-hydroxy-5-(4-phenylphenyl)pentanamide
• CAS: 191228-43-0
• 化学式: C₁₇H₁₉NO₂
• 分子量: 269.343
• InChiKey: QQLOLMJSVXGPGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-(4-联苯)吉草酸 在 盐酸羟胺 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以62%的产率得到5-(biphenyl-4-yl)-pentanoic acid N-hydroxyamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors

  摘要：

  A series of hydroxamic acid-based histone deacetylase (HDAC) inhibitors were designed on the basis of a model of the HDAC2 binding site and synthesized. They are characterized by a cinnamic spacer, capped with a substituted phenyl group. Modifications of the spacer are also reported. In an in vitro assay with the isoenzyme HDAC2, a good correlation of the activity with the docking energy was found. In human ovarian carcinoma IGROV-1 cells, selected compounds produced significant acetylation of p53 and alpha-tubulin. Most compounds showed an antiproliferative activity comparable to that of SAHA. At equitoxic concentrations, the tested compounds were more effective than SAHA in inducing apoptotic cell death. Compounds selected for in vivo evaluation exhibited a significant antitumor activity on three tumor models at well tolerated doses, thus suggesting a good therapeutic index. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.11.005

文献信息

• BIPHENYL HYDROXAMATE INHIBITORS OF MATRIX METALLOPROTEINASES
  申请人：Abbott Laboratories

  公开号：EP0874808A1

  公开（公告）日：1998-11-04
• US5665777A
  申请人：——

  公开号：US5665777A

  公开（公告）日：1997-09-09
• [EN] BIPHENYL HYDROXAMATE INHIBITORS OF MATRIX METALLOPROTEINASES<br/>[FR] INHIBITEURS DE METALLOPROTEINASES MATRICIELLES, A L'HYDROXAMATE BIPHENYLIQUE
  申请人：ABBOTT LABORATORIES

  公开号：WO1997018188A1

  公开（公告）日：1997-05-22

  (EN) Compounds of formula (I), or a pharmaceutically acceptable salt thereof inhibit matrix metalloproteinases and TNF$g(a) secretion and are useful in the treatment of inflammatory disease states. Also disclosed are matrix metalloproteinases and TNF$g(a) secretion inhibiting compositions and a method for inhibiting matrix metalloproteinases and TNF$g(a) secretion.(FR) L'invention concerne des composés de formule (I) ou un sel pharmaceutiquement acceptable de ceux-ci, qui inhibent la sécrétion des métalloprotéinases matricielles et de TNF$g(a) et sont utiles dans le traitement de pathologies inflammatoires. Elle porte aussi sur des compositions inhibant la sécrétion de métalloprotéinases matricielles et de TNF$g(a) et sur une méthode d'inhibition de la sécrétion de métalloprotéinases matricielles et de TNF$g(a).
• Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors
  作者：Sabrina Dallavalle、Raffaella Cincinelli、Raffaella Nannei、Lucio Merlini、Gabriella Morini、Sergio Penco、Claudio Pisano、Loredana Vesci、Marcella Barbarino、Valentina Zuco

  DOI：10.1016/j.ejmech.2008.11.005

  日期：2009.5

  A series of hydroxamic acid-based histone deacetylase (HDAC) inhibitors were designed on the basis of a model of the HDAC2 binding site and synthesized. They are characterized by a cinnamic spacer, capped with a substituted phenyl group. Modifications of the spacer are also reported. In an in vitro assay with the isoenzyme HDAC2, a good correlation of the activity with the docking energy was found. In human ovarian carcinoma IGROV-1 cells, selected compounds produced significant acetylation of p53 and alpha-tubulin. Most compounds showed an antiproliferative activity comparable to that of SAHA. At equitoxic concentrations, the tested compounds were more effective than SAHA in inducing apoptotic cell death. Compounds selected for in vivo evaluation exhibited a significant antitumor activity on three tumor models at well tolerated doses, thus suggesting a good therapeutic index. (C) 2008 Elsevier Masson SAS. All rights reserved.