(2E,4E,6E,8E)-N-(3-chloro-4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenamide

• 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: (2E,4E,6E,8E)-N-(3-chloro-4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenamide
• 英文别名: (2E,4E,6E,8E)-N-(3-chloro-4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenamide
• 化学式: C₂₆H₃₂ClNO₂
• 分子量: 425.999
• InChiKey: VZDPAYQFJHNFDN-HPWKXKAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  维A酸 在 吡啶 、 六氯丙酮 、 triphenylphosphine-resin 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 (2E,4E,6E,8E)-N-(3-chloro-4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenamide
  参考文献：
  名称：

  Solid phase-assisted synthesis and screening of a small library of N-(4-hydroxyphenyl)retinamide (4-HPR) analogs

  摘要：

  Using solid phase-assisted synthesis and purification, a 49 member library of analogs of the main mammary tumor chemopreventive retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been prepared. After prescreening for growth inhibitory activity in human mammary tumor cells (MCF-7) in culture, most of those analogs which showed activity (12 of them) were assayed for apoptosis-inducing activity in the MCF-7 cells. At least 3 of the analogs (13, 24, and 28) showed activity approaching that of 4-HPR. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.050

文献信息

• Design, Synthesis, Radiosynthesis and Biological Evaluation of Fenretinide Analogues as Anticancer and Metabolic Syndrome‐Preventive Agents
  作者：Ilaria Patruno、Dawn Thompson、Sergio Dall'Angelo、Albert D. Windhorst、Danielle J. Vugts、Alex J. Poot、Nimesh Mody、Matteo Zanda

  DOI：10.1002/cmdc.202000143

  日期：2020.8.19

  describe the preparation of a library of 4‐HPR analogues, followed by the biological evaluation of their anti‐cancer and anti‐obesity/diabetic properties. The click‐type analogue 3 b showed good capacity to reduce the amount of lipid accumulation in 3T3‐L1 adipocytes during differentiation. Furthermore, it showed an IC50 of 0.53±0.8 μM in cell viability tests on breast cancer cell line MCF‐7, together

  Fenretinide（4-HPR）是全反式视黄酸（ATRA）的合成衍生物，具有相对于ATRA更高的治疗特性和毒理学特征。4-HPR作为抗癌药已被广泛研究，但最近的研究表明，4-HPR在预防代谢综合征方面具有广阔的前景。4-HPR的活性涉及多个生物学靶标，导致该分子可能用于治疗不同的病理学。然而，尽管4-HPR在药理学方面显示出了很好理解的多靶点混杂性，但解释其确切的生理作用仍然具有挑战性。此外，尽管体外试验结果令人满意，到目前为止，4-HPR作为化学治疗剂的临床疗效尚不令人满意。本文中，我们描述了4-HPR类似物文库的制备，然后对其抗癌和抗肥胖/糖尿病特性进行了生物学评估。点击型类似物3b在分化过程中显示出良好的能力来减少3T3-L1脂肪细胞中脂质的积累。此外，在乳腺癌细胞系MCF-7的细胞活力测试中，IC 50为0.53±0.8μM，并且对非癌性HEK293细胞具有良好的选择性（SI =
• Solid phase synthesis of arylretinamides
  申请人：——

  公开号：US20030105164A1

  公开（公告）日：2003-06-05

  A solid phase synthetic method for preparing arylretinamides is provided. The method comprises reacting hexachloroacetone with a solvent-suspended resin-bound triphenylphosphine to provide a suspension comprising an activated chlorinating reagent; reacting retinoic acid with the activated chlorinating reagent to provide retinoyl chloride; adding pyridine and a select arylamine to the resulting mixture; and stirring the resulting mixture for a time and at a temperature sufficient for the select arylamine to react with the retinoyl chloride and provide the arylretinamide. Also provided, are select arylretinamides that can be prepared by the present method, and methods of using such arylretinamides to induce apoptosis in cancer cells.

  提供了一种用于制备芳基维甲酰胺的固相合成方法。该方法包括将六氯乙酮与悬浮于溶剂中的树脂结合的三苯基膦反应，以提供含有活化氯化试剂的悬浮液；将维甲酸与活化氯化试剂反应以提供维甲酰氯；向得到的混合物中加入吡啶和选择的芳基胺；并在足够时间和温度下搅拌得到的混合物，以使选择的芳基胺与维甲酰氯反应并提供芳基维甲酰胺。还提供了可以通过该方法制备的选择性芳基维甲酰胺，以及使用这些芳基维甲酰胺在癌细胞中诱导凋亡的方法。
• FENRETINIDE DERIVATIVES AND USES THEREOF AS THERAPEUTIC, DIAGNOSTIC AND IMAGING AGENTS
  申请人：Kalpana Ganjam V.

  公开号：US20110091383A1

  公开（公告）日：2011-04-21

  Synthetic peptidomimetic derivatives and phenyl group derivatives of Fenretinide (4-HPR) are disclosed, as are their uses as therapeutic, diagnostic and imaging agents for cancer and other diseases.

  本发明涉及Fenretinide（4-HPR）的合成肽类模拟衍生物和苯基衍生物，以及它们作为治疗、诊断和肿瘤及其他疾病成像剂的用途。
• US6696606B2
  申请人：——

  公开号：US6696606B2

  公开（公告）日：2004-02-24
• US7550510B2
  申请人：——

  公开号：US7550510B2

  公开（公告）日：2009-06-23