(2E,4E,6Z,8Z)-8-(3,4-dihydro-1(2H)-naphthalen-1-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid | 205252-57-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (2E,4E,6Z,8Z)-8-(3,4-dihydro-1(2H)-naphthalen-1-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid
• 英文别名: (2E,4E,6Z,8E)-8-(3,4-dihydronaphthalen-1(2H)-ylidene)-3,7-dimethylocta-2,4,6-trienoic acid；(9Z)-UAB30；(2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid；Retinoid 9CUAB30；(2E,4E,6Z,8E)-8-(3,4-dihydro-2H-naphthalen-1-ylidene)-3,7-dimethylocta-2,4,6-trienoic acid
• CAS: 205252-57-9
• 化学式: C₂₀H₂₂O₂
• 分子量: 294.393
• InChiKey: PPGNMFUMZSAZCW-VOYUZAMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  3-甲基-4-膦酰丁烯酸三乙酯 在 六甲基磷酰三胺 、 氢氧化钾 、 sodium hydride 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 (2E,4E,6Z,8Z)-8-(3,4-dihydro-1(2H)-naphthalen-1-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid
  参考文献：
  名称：

  Conformationally Defined Retinoic Acid Analogues. 4. Potential New Agents for Acute Promyelocytic and Juvenile Myelomonocytic Leukemias

  摘要：

  We recently synthesized several conformationally constrained retinoic acid (RA) analogues [8-(2'-cyclohexen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acids with different alkyl substituents at 2' (R-1) and 3' (R-2) positions on the cyclohexene ring] (Muccio et al. J. Med. Chem. 1996, 39, 3625) as cancer chemopreventive agents. UAB8 (R-1 = Et; R-2 = Pr-i), which contains sufficient steric bulk at the terminal end of the polyene chain to mimic the trimethylcyclohexenyl ring of RA, displayed biological properties similar to those of RA. To explore the efficacy of this retinoid in acute promyelocytic leukemia (APL) and juvenile myelomonocytic leukemia (JMML), we evaluated UAB8 isomers in in vitro assays which measure the capacity of retinoids to inhibit aberrant myeloid colony growth from blood or bone marrow cells obtained from human JMML patients and in assays measuring the potential of retinoids to differentiate NB4 cells tan APL cell line). Both (all-E)- and (13Z)-UAB8 were 2-fold more active than RA in the NB4 cell differentiation assay; however, only (all-E)-UAB8 had comparable activity to the natural retinoids in the JMML cell assays. These results were compared to the biological effectiveness of a new retinoid, UAB30 [8-(3',4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid], which had different nuclear receptor binding and transactivational properties than UAB8. Relative to (all-E)-RA and (all-E)-UAB8, (all-E)-UAB30 bound well to RAR alpha but did not activate transcription-mediated RAR alpha homodimers, even though it was effective in RAR beta- and RAR gamma-mediated transactivational assays. In APL assays, this retinoid had much reduced activity and was only moderately effective in JMML assays and in cancer chemoprevention assays.

  DOI：

  10.1021/jm970635h

文献信息

• [EN] PROCESS FOR THE SYNTHESIS OF (2E, 4E, 6Z, 8E)-8-(3,4-DIHYDRONAPHTHALEN-1(2H)-YLIDENE)-3,7-DIMETHYLOCTA-2, 4, 6-TRIENOIC ACID<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE L'ACIDE (2E, 4E, 6Z, 8E)-8-(3,4-DIHYDRONAPHTHALEN-1(2H)-YLIDÈNE)-3,7-DIMÉTHYLOCTA-2,4,6-TRIÉNOÏQUE
  申请人：MERZ PHARMACEUTICALS LLC

  公开号：WO2017158023A1

  公开（公告）日：2017-09-21

  This invention relates to a novel method for the synthesis of (2E,4E,6Z,8E)-8-(3,4- dihydronaphthalen-1 (2H)-ylidene)-3,7-dimethylocta-2,4,6-trienoic acid. In particular, the invention relates to several improvements in several individual steps of the multi- step synthesis scheme

  本发明涉及一种合成(2E,4E,6Z,8E)-8-(3,4-二氢萘-1(2H)-亚基)-3,7-二甲基-2,4,6-辛三烯酸的新方法。特别是，本发明涉及在多步合成方案中的几个单独步骤的几项改进。
• [EN] NOVEL BEXAROTENE ANALOGS<br/>[FR] ANALOGUES INÉDITS DU BEXAROTÈNE
  申请人：UNIV ARIZONA

  公开号：WO2011103321A1

  公开（公告）日：2011-08-25

  The present invention relates to analogs of bexarotene and methods of use thereof.

  本发明涉及贝沙罗汀的类似物及其使用方法。
• THERAPEUTIC COMPOUNDS
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US20180072697A1

  公开（公告）日：2018-03-15

  The invention provides compounds formula (I) and salts thereof: wherein the bond represented by ---- is a single bond or a double bond, and R1 has any of the values defined in the specification. The compounds are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.

  该发明提供了化合物公式（I）及其盐：其中由 ---- 表示的键是单键或双键，R1具有规范中定义的任何值。这些化合物可用于治疗包括阿尔茨海默病、帕金森病、糖尿病、癌症以及精神分裂症等疾病。
• Methods for making retinoids and uses thereof
  申请人：The UAB Research Foundation

  公开号：US09169190B2

  公开（公告）日：2015-10-27

  Described herein are methods for making retinoids. Also described herein are retinoids and methods of use thereof.

  本文描述了制备维甲酸类化合物的方法。同时也描述了维甲酸类化合物的性质及其使用方法。
• METHODS FOR MAKING RETINOIDS AND USES THEREOF
  申请人：The UAB Research Foundation

  公开号：US20160106697A1

  公开（公告）日：2016-04-21

  Described herein are methods for making retinoids. Also described herein are retinoids and methods of use thereof.

  本文描述了制备视黄醇的方法。同时还描述了视黄醇及其使用方法。