E-3-chloro-4-hydroxyphenylcinnamic acid | 862651-13-6

• 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: E-3-chloro-4-hydroxyphenylcinnamic acid
• 英文别名: (E)-3-[4-(3-chloro-4-hydroxyphenyl)phenyl]prop-2-enoic acid
• CAS: 862651-13-6
• 化学式: C₁₅H₁₁ClO₃
• 分子量: 274.704
• InChiKey: JYQUUXCBSFIDSS-FPYGCLRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  E-3-chloro-4-hydroxyphenylcinnamic acid 在 盐酸羟胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以24%的产率得到N-hydroxy-(E)-3-[3'-chloro-4'-hydroxybiphenyl-4-yl]-acrylamide
  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
• 作为产物：
  描述：

  4-溴-2-氯苯酚 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 lithium hydroxide 、 potassium acetate 、 联硼酸频那醇酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 E-3-chloro-4-hydroxyphenylcinnamic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of a New Series of Retinoid-Related Biphenyl-4-ylacrylic Acids Endowed with Antiproliferative and Proapoptotic Activity

  摘要：

  Atypical retinoids (AR) represent a class of proapoptotic agents with promising potential in the treatment of neoplastic diseases. In the present work 4'-hydroxybiphenyl-4-ylacrylic acids were studied as a novel series of AR. The synthesized compounds were evaluated for their antiproliferative activity in a human promyelocytic leukemia cell line (NB4) and in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild-type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of a bulky lipophilic group at position 3' (adamantan-1-yl being the best) and the E configuration of the acrylic moiety appear essential for activity below 1 mu M. No substitution on the rings or on the double bond improved the activity. A qualitative correlation between the log P and molecular volume of the 3'-substituent and the antiproliferative activity was found. From the study of a few selected compounds, it appears that the presence of the carboxylic group is an essential requirement for apoptogenic properties but not for antiproliferative activity, this being maintained in amide derivatives. On the other hand, compounds able to induce apoptosis produced a detectable level of genotoxic damage. This observation supports the hypothesis that the genotoxic stress is a critical event mediating apoptosis induction by compounds of this class. Among the compounds investigated, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (2) was chosen for further investigation.

  DOI：

  10.1021/jm049440h

文献信息

• Biphenyl and Naphthyl-Phenyl Hydroxamic Acid Derivatives
  申请人：Pisano Claudio

  公开号：US20080319082A1

  公开（公告）日：2008-12-25

  Biphenyl and phenyl-naphthyl compounds bearing a hydroxamic group, which are endowed with antitumour, and anti-angiogenic activity These compounds are therefore particularly useful for the treatment of drug-resistant tumours.

  苯基联苯和苯基萘化合物带有羟肟基，具有抗肿瘤和抗血管生成活性。因此，这些化合物特别适用于治疗耐药性肿瘤。
• WO2007/383
  申请人：——

  公开号：——

  公开（公告）日：——
• US7728039B2
  申请人：——

  公开号：US7728039B2

  公开（公告）日：2010-06-01
• [EN] BIPHENYL AND NAPHTHYL-PHENYL HYDROXAMIC ACID DERIVATIVES<br/>[FR] DÉRIVÉS D'ACIDES HYDROXAMIQUES BIPHÉNYLES ET NAPHTHYLES-PHÉNYLES
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2007000383A1

  公开（公告）日：2007-01-04

  [EN] Biphenyl and phenyl-naphthyl compounds bearing a hydroxamic group, which are endowed with antitumour, and anti-angiogenic activity These compounds are therefore particularly useful for the treatment of drug-resistant tumours.
  [FR] La présente invention concerne des composés biphényles et phényles-naphthyles portant un groupe hydroxamique, qui présentent des activités antitumorales et antiangiogenèses. Ainsi, ces composés se révèlent particulièrement utiles lors du traitement de tumeurs résistant aux médicaments.
• Synthesis and Structure−Activity Relationships of a New Series of Retinoid-Related Biphenyl-4-ylacrylic Acids Endowed with Antiproliferative and Proapoptotic Activity
  作者：Raffaella Cincinelli、Sabrina Dallavalle、Raffaella Nannei、Serena Carella、Daniele De Zani、Lucio Merlini、Sergio Penco、Enrico Garattini、Giuseppe Giannini、Claudio Pisano、Loredana Vesci、Paolo Carminati、Valentina Zuco、Chiara Zanchi、Franco Zunino

  DOI：10.1021/jm049440h

  日期：2005.7.1

  Atypical retinoids (AR) represent a class of proapoptotic agents with promising potential in the treatment of neoplastic diseases. In the present work 4'-hydroxybiphenyl-4-ylacrylic acids were studied as a novel series of AR. The synthesized compounds were evaluated for their antiproliferative activity in a human promyelocytic leukemia cell line (NB4) and in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild-type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of a bulky lipophilic group at position 3' (adamantan-1-yl being the best) and the E configuration of the acrylic moiety appear essential for activity below 1 mu M. No substitution on the rings or on the double bond improved the activity. A qualitative correlation between the log P and molecular volume of the 3'-substituent and the antiproliferative activity was found. From the study of a few selected compounds, it appears that the presence of the carboxylic group is an essential requirement for apoptogenic properties but not for antiproliferative activity, this being maintained in amide derivatives. On the other hand, compounds able to induce apoptosis produced a detectable level of genotoxic damage. This observation supports the hypothesis that the genotoxic stress is a critical event mediating apoptosis induction by compounds of this class. Among the compounds investigated, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (2) was chosen for further investigation.