4,5-didehydro-5,6-dihydroretinoic acid | 58526-49-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 4,5-didehydro-5,6-dihydroretinoic acid
• 英文别名: (2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-2-enyl)nona-2,4,6,8-tetraenoic acid；(2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-2-en-1-yl)nona-2,4,6,8-tetraenoic acid
• CAS: 58526-49-1
• 化学式: C₂₀H₂₈O₂
• 分子量: 300.441
• InChiKey: ILLYYNHLCANIBL-XFYACQKRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  亚异丙基丙二酸二甲酯 在 2,6-二甲基吡啶 、 sodium hydroxide 、 苄基三甲基氢氧化铵 作用下， 以 甲醇 、 水 为溶剂， 反应 22.0h， 生成 4,5-didehydro-5,6-dihydroretinoic acid
  参考文献：
  名称：

  通过β-亚甲基醛作为合成子立体选择性合成13 Z Z视黄酸

  摘要：

  描述了经由β-亚甲基醛的13Z视黄酸的立体选择性合成。在亚甲基-脱氧-双取代反应（Knoevenagel，Stobbe等）中，这些新的合成子产生立体选择性的E烯烃。因此，描述了通过羧基-14-视黄酸的立体有择的单脱羧作用来合成13Z视黄酸。

  DOI：

  10.1016/s0040-4039(99)01963-2

文献信息

• Stereoselective Synthesis of Trienoic Acids: Synthesis of Retinoic Acids and Analogues
  作者：Jérôme Thibonnet、Mohamed Abarbri、Jean-Luc Parrain、Alain Duchêne

  DOI：10.1055/s-2006-950201

  日期：2006.9

  Stereoselective construction of conjugated trienoic acids was achieved through two successive Stille reactions, the first step consisting of the coupling of (E)-1,2-bis(tributylstannyl)ethene and tributylstannyl (Z)- or (E)-3-iodoalk-2-enoates. Two different routes were used for the second step: (1) cross-coupling of the stannyldienoic acid reagents and vinyl iodides, or (2) cross-coupling of vinylstannane

  通过两个连续的 Stille 反应实现共轭三烯酸的立体选择性构建，第一步包括 (E)-1,2-双(三丁基甲锡烷基)乙烯和三丁基甲锡烷基 (Z)- 或 (E)-3-iodoalk- 的偶联2-烯酸。第二步使用了两种不同的途径：(1) 甲锡基二烯酸试剂和乙烯基碘化物的交叉偶联，或 (2) 乙烯基锡烷试剂和通过碘脱苯甲酸化生成的 5-碘戊二烯酸三丁基甲锡酯的交叉偶联的亚锡烷基。通过衍生自 β-或 α-紫罗兰酮和番红醛的 Negishi 二烯的亚锡基金属化合成的乙烯基锡烷提供了获得立体定义的视黄酸的途径。还通过 Sonogashira 偶联制备了一些类视黄醇和 yne 类似物。
• New, Regioselective, One-Pot Synthesis of (all-E)-Retinoic Acid and Analogues from Enaminodiester Synthons
  作者：Dominique Cartier、Alain Valla、Régis Le Guillou、Roger Labia、Pierre Potier

  DOI：10.1002/ejoc.200300029

  日期：2003.6

  one-pot synthesis of (all-E)-retinoic acid and related compounds from new enamino diester synthons is described. The enamino diesters was produced nearly quantitatively from methyl propylidene- and isopropylidenemalonate and DMF−DMA. This easy process allowed retinoic acid to be produced in 1 d and appeared advantageous to current industrial syntheses. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim

  描述了从新的烯氨基二酯合成子一锅合成 (all-E)-视黄酸和相关化合物。烯氨基二酯几乎定量地从亚丙基丙二酸甲酯和异亚丙基丙二酸酯以及 DMF-DMA 中产生。这种简单的过程允许在 1 d 内生产视黄酸，并且似乎有利于当前的工业合成。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
• Methods and compositions for the treatment of proliferative disorders
  申请人：Beth Israel Deaconess Medical Center, Inc.

  公开号：US10265288B2

  公开（公告）日：2019-04-23

  The invention features methods of treating a proliferative disorder characterized by elevated Pin1 marker levels and/or reduced Pin1 Ser71 phosphorylation in a subject by administering a retinoic acid compound. Additionally, the invention features methods of treating proliferative disorders (e.g., proliferative disorders characterized by elevated Pin1 marker levels) by administering a retinoic acid compound in combination with another anti-proliferative compound. Finally, the invention also features methods including high-throughput screens for discovering and validating Pin1 inhibitors.

  本发明的特点是通过施用维甲酸化合物治疗增殖性疾病的方法，该增殖性疾病的特征是受试者体内Pin1标记物水平升高和/或Pin1 Ser71磷酸化降低。此外，本发明还具有通过施用维甲酸化合物与另一种抗增殖化合物联合治疗增殖性疾病（例如，以Pin1标记物水平升高为特征的增殖性疾病）的方法。最后，本发明还包括发现和验证 Pin1 抑制剂的高通量筛选方法。
• Enhanced ATRA-related compounds for the treatment of proliferative diseases, autoimmune diseases, and addiction conditions
  申请人：Beth Israel Deaconess Medical Center, Inc.

  公开号：US10548864B2

  公开（公告）日：2020-02-04

  The invention features all-trans retinoic acid (ATRA)-related compounds capable of associating with Pin1 and methods of treating a proliferative disorder characterized by elevated Pin1 marker levels, Pin1 degradation, and/or reduced Pin1 Ser71 phosphorylation in a subject by administering an ATRA-related compound. The invention also features methods of treating proliferative disorders, autoimmune diseases, and addiction conditions (e.g., diseases, disorders, and conditions characterized by elevated Pin1 marker levels) by administering an ATRA-related compound in combination with another therapeutic compound.

  本发明的特征是能够与Pin1结合的全反式维甲酸（ATRA）相关化合物，以及通过施用ATRA相关化合物治疗以Pin1标记物水平升高、Pin1降解和/或Pin1 Ser71磷酸化降低为特征的增殖性疾病的方法。本发明的另一个特点是通过施用 ATRA 相关化合物与另一种治疗化合物联合治疗增殖性疾病、自身免疫性疾病和成瘾病症（例如，以 Pin1 标记水平升高为特征的疾病、病症和病症）的方法。
• Arsenic trioxide for treatment of PIN1-associated disorders
  申请人：Beth Israel Deaconess Medical Center, Inc.

  公开号：US10980835B2

  公开（公告）日：2021-04-20

  The present invention relates to the treatment of Pin1-associated disorders (e.g., disorders characterized by elevated Pin1 activity) with arsenic trioxide, optionally in combination with a retinoic acid compound. Pin1-associated disorders may include, for example, proliferative disorders (e.g., cancers), inflammatory conditions, and autoimmune disorders associated with aberrant levels of Pin1 activity.

  本发明涉及用三氧化二砷治疗Pin1相关疾病（例如，以Pin1活性升高为特征的疾病），可选择与维甲酸化合物联合使用。Pin1相关疾病可包括与Pin1活性异常水平相关的增殖性疾病（如癌症）、炎症和自身免疫性疾病等。