13-cis-14-Methylretinoic acid | 138231-97-7

• 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: 13-cis-14-Methylretinoic acid
• 英文别名: (2Z,4E,6E,8E)-2,3,7-trimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid
• CAS: 138231-97-7
• 化学式: C₂₁H₃₀O₂
• 分子量: 314.468
• InChiKey: JBPFZFHPMYJRDQ-QTNYDBDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.48
• 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：

  14-Methyl-20,14-retro-retinoic acid 在 18-冠醚-6 、 sodium t-butanolate 作用下， 以 乙醚 、 叔丁醇 为溶剂， 反应 3.83h， 生成 13-cis-14-Methylretinoic acid
  参考文献：
  名称：

  视黄酸的碱催化异构化。14-烷基化的全反式，13-顺式和20,14-复古-视黄酸的合成和诱导分化的活性。

  摘要：

  视黄酸（1）通过过量的二异丙基氨基锂（LDA）进行区域选择性异构化，得到20,14-复古视黄酸（3）。视黄酸的中间二价阴离子的烷基化得到3的14-烷基化衍生物。通过在碱性条件下烷基化的逆向异构体的异构化，合成了几种14-烷基-全反式和-13-顺式-视黄酸。基于诱导人早幼粒细胞白血病细胞系HL-60分化的能力，检查了这些衍生物的类维生素A活性。20,14-复古视黄酸（3）的活性是视黄酸（1）的1/50。虽然14-甲基-20,14-复古-视黄酸（4）具有3的活性，但将14-甲基引入全反式和13-顺式-视黄酸会降低活性。

  DOI：

  10.1021/jm00081a020

文献信息

• 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。
• METHODS AND COMPOSITIONS FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：Lu Kun Ping

  公开号：US20140086909A1

  公开（公告）日：2014-03-27

  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.
• ENHANCED ATRA-RELATED COMPOUNDS DERIVED FROM STRUCTURE-ACTIVITY RELATIONSHIPS AND MODELING FOR INHIBITING PIN1
  申请人：Beth Israel Deaconess Medical Center, Inc.

  公开号：US20170112792A1

  公开（公告）日：2017-04-27

  The invention features all-trans retinoic acid (ATRA)-related compounds capable of associating with Pin1 and methods of identifying the same. The invention also provides methods of treating a condition selected from the group consisting of a proliferative disorder, an autoimmune disease, and an addiction condition characterized by elevated Pin1 marker levels, Pin1 degradation, and/or reduced Pin1 Ser71 phosphorylation in a subject by administering a retinoic acid compound. Additionally, the invention 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 a retinoic acid compound in combination with another therapeutic compound. The invention also features a co-crystal including Pin1 and a retinoic acid compound. Finally, the invention also provides methods of developing and identifying enhanced Pin1-targeted ATRA-related compounds based on the newly defined unique binding pockets in the Pin1 active site revealed from the co-crystal structure, structure-activity relationship, and structural modeling.