methyl E-3-(4'-hydroxy-3'-(1-methylcyclohexyl)biphenyl-4-yl)acrylate | 496858-48-1

• 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: methyl E-3-(4'-hydroxy-3'-(1-methylcyclohexyl)biphenyl-4-yl)acrylate
• 英文别名: methyl (E)-3-[4-[4-hydroxy-3-(1-methylcyclohexyl)phenyl]phenyl]prop-2-enoate
• CAS: 496858-48-1
• 化学式: C₂₃H₂₆O₃
• 分子量: 350.458
• InChiKey: RZCCZNVVJHXGPK-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl E-3-(4'-hydroxy-3'-(1-methylcyclohexyl)biphenyl-4-yl)acrylate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以48%的产率得到(E)-3-[4-[4-hydroxy-3-(1-methylcyclohexyl)phenyl]phenyl]prop-2-enoic 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
• 作为产物：
  描述：

  1-甲基环己醇 在 palladium diacetate 、 硫酸 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 二氯甲烷 为溶剂， 反应 98.0h， 生成 methyl E-3-(4'-hydroxy-3'-(1-methylcyclohexyl)biphenyl-4-yl)acrylate
  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

• [EN] RETINOID DERIVATIVES WITH ANTIANGIOGENIC, ANTITUMORAL AND PROAPOPTOTIC ACTIVITIES<br/>[FR] DERIVES RETINOIDES A ACTIVITE ANTIANGIOGENIQUE, ANTITUMORALE ET PROAPOPTOTIQUE
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2003011808A1

  公开（公告）日：2003-02-13

  Are described compounds of Formula (I) in which R, R', R'', A, and D have the meanings described in the text, as useful agents in the cure of pathologies characterised by altered angiogenesis and as antitumorals.

  描述了式(I)中的化合物，其中R、R'、R''、A和D的含义如文本所述，作为治疗具有改变血管生成的病理和抗肿瘤药物的有用剂型。
• Retinoid derivatives with antiangiogenic, antitumoral and proapoptotic activities
  申请人：——

  公开号：US20040235757A1

  公开（公告）日：2004-11-25

  Are described compounds of Formula (I) in which R, R′, R″, A, and D have the meanings described in the text, as useful agents in the cure of pathologies characterised by altered angiogenesis and as antitumorals.

  化合物的公式（I）中的R，R'，R''，A和D的含义如文本所述，可用作治疗具有改变的血管生成的病理特征和抗肿瘤剂的有用药剂。
• Retinoid Derivatives With Antiangiogenic, Antitumoral And Proapoptotic Activities
  申请人：Dallavalle Sabrina

  公开号：US20080021088A1

  公开（公告）日：2008-01-24

  Described and claimed are compounds of Formula (I) in which R, R′, R″, A, and D have the meanings described in the text, as useful agents in the cure of pathologies characterized by altered angiogenesis and as antitumorals.

  描述和声明的是化合物式（I）的化合物，其中R、R'、R"、A和D在文本中所描述的含义，作为治疗由异常血管生成特征的病理状况和抗肿瘤剂的有用药物。
• RETINOID DERIVATIVES WITH ANTIANGIOGENIC, ANTITUMOR AND PROAPOPTOTIC ACTIVITIES
  申请人：SIGMA-TAU IndustrieFarmaceutiche Riunite S.p.A.

  公开号：EP1412317A1

  公开（公告）日：2004-04-28
• COMBINATION OF A RETINOID AND A PLATINUM ANTICANCER AGENT
  申请人：SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.

  公开号：EP2101820A2

  公开（公告）日：2009-09-23