1,4-Bis[(3,4,5-trihydroxybenzoyl)oxy]-5,6,7,8-tetrahydronaphthalene

• 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: 1,4-Bis[(3,4,5-trihydroxybenzoyl)oxy]-5,6,7,8-tetrahydronaphthalene
• 英文别名: [4-(3,4,5-trihydroxybenzoyl)oxy-5,6,7,8-tetrahydronaphthalen-1-yl] 3,4,5-trihydroxybenzoate
• 化学式: C₃₄H₂₇N₄O₇PolS
• 分子量: 468.4
• InChiKey: PBJKPIIRGAZPET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  174
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1,4-Bis[(3,4,5-trihydroxybenzoyl)oxy]-5,6,7,8-tetrahydronaphthalene 、 trans-1,2-cyclohexandiol 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以50%的产率得到trans-1,2-bis([3,4,5-tris(benzyloxy)benzoyl]oxy)cyclohexane
  参考文献：
  名称：

  New Synthetic Inhibitors of Fatty Acid Synthase with Anticancer Activity

  摘要：

  Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds 5-30 that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with art IC50 < 50 mu M have been tested for their ability to inhibit FASN activity. Among them, derivative 30 blocks the 90% of FASN activity at low concentration (4 mu M), is highly cytotoxic in a broad panel of tumor cells, induces apoptosis, and blocks the activation of HER2, AKT, and ERK pathways. Remarkably, 30 does not activate carnitine palmitoyltransferase-1 (CPT-1) nor induces in mice weight loss, which are the main drawbacks of other previously described FASN inhibitors. Thus, FASN inhibitor 30 may aid the validation of this enzyme as a therapeutic target for the treatment of cancer.

  DOI：

  10.1021/jm2016045
• 作为产物：
  描述：

  1,4-二羟基萘 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 生成 1,4-Bis[(3,4,5-trihydroxybenzoyl)oxy]-5,6,7,8-tetrahydronaphthalene
  参考文献：
  名称：

  New Synthetic Inhibitors of Fatty Acid Synthase with Anticancer Activity

  摘要：

  Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds 5-30 that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with art IC50 < 50 mu M have been tested for their ability to inhibit FASN activity. Among them, derivative 30 blocks the 90% of FASN activity at low concentration (4 mu M), is highly cytotoxic in a broad panel of tumor cells, induces apoptosis, and blocks the activation of HER2, AKT, and ERK pathways. Remarkably, 30 does not activate carnitine palmitoyltransferase-1 (CPT-1) nor induces in mice weight loss, which are the main drawbacks of other previously described FASN inhibitors. Thus, FASN inhibitor 30 may aid the validation of this enzyme as a therapeutic target for the treatment of cancer.

  DOI：

  10.1021/jm2016045

文献信息

• Novel Polyhydroxylated Compounds as Fatty Acid Synthase (FASN) Inhibitors
  申请人：Colomer Bosch Ramón

  公开号：US20100190856A1

  公开（公告）日：2010-07-29

  The present invention relates to new polyhydroxylated compounds and, in particular, to its activity as fatty acid synthase (FASN) inhibitors and to their use for the treatment of pathological states for which an inhibitor of this enzyme is indicated. The invention further relate to pharmaceutical compositions containing them and to a process for the preparation of such compounds.

  本发明涉及新的多羟基化合物，特别是它们作为脂肪酸合成酶（FASN）抑制剂的活性以及它们用于治疗需要该酶抑制剂的病理状态。本发明还涉及含有它们的制药组合物以及制备这些化合物的方法。
• [EN] NOVEL POLYHYDROXYLATED COMPOUNDS AS FATTY ACID SYNTHASE (FASN) INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS POLYHYDROXYLÉS COMME INHIBITEURS D'ACIDE GRAS SYNTHASES (FASN)
  申请人：FUNDACIO PRIVADA INST D INVEST

  公开号：WO2009000864A1

  公开（公告）日：2008-12-31

  [EN] The present invention relates to new polyhydroxylated compounds and, in particular, to its activity as fatty acid synthase (FASN) inhibitors and to their use for the treatment of pathological states for which an inhibitor of this enzyme is indicated. The invention further relate to pharmaceutical compositions containing them and to a process for the preparation of such compounds.
  [FR] La présente invention porte sur de nouveaux composés polyhydroxylés et, en particulier, sur leur activité comme inhibiteurs d'acide gras synthase (FASN) et sur leur utilisation pour le traitement d'états pathologiques pour lesquels un inhibiteur de cette enzyme est indiqué. L'invention concerne en outre les compositions pharmaceutiques les contenant et un procédé pour la préparation de tels composés.