trans-2,3-dimethoxystilbene | 122950-70-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: trans-2,3-dimethoxystilbene
• 英文别名: (E)-2,3-dimethoxystilbene；(E)-3-fluorostilbene；1,2-dimethoxy-3-[(E)-2-phenylethenyl]benzene
• CAS: 122950-70-3
• 化学式: C₁₆H₁₆O₂
• 分子量: 240.302
• InChiKey: LBCIRZACLFULBJ-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  trans-2,3-dimethoxystilbene 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以82%的产率得到(E)-2,3-dihydroxystilbene
  参考文献：
  名称：

  Synthesis and Nematocidal Activity of Hydroxystilbenes

  摘要：

  通过一种新的(Z)-(E)异构化方法随后进行脱甲基反应，从(E)/(Z)混合甲氧基二苯乙烯中合成了多种(E)-羟基二苯乙烯。当甲氧基二苯乙烯脱甲基生成羟基二苯乙烯时，表现出杀线虫活性。为了产生这种活性，C-2或C-3位置上必须有一个羟基。因此，2-羟基-、3-羟基-、2,6-二羟基-、3,4-二羟基-、3,5-二羟基-、2,2'-二羟基-、3,3'-二羟基-、3,4'-二羟基-、2-羟基-4-甲氧基-、5-羟基-2-甲氧基-、2-羟基-6-甲氧基-、6-烯丙氧基-2-羟基-、3-羟基-5-甲氧基-和5-烯丙氧基-3-羟基二苯乙烯表现出相当强的杀线虫活性。5-烯丙氧基-3-羟基二苯乙烯的活性最强[最小致死浓度（MLC）=30 μM]。(E)和(Z)异构体的活性相当。二氢衍生物，羟基联苄中也保留了这些活性，尽管较弱。

  DOI：

  10.1248/cpb.40.1130
• 作为产物：
  描述：

  溴甲苯 、 2,3-二甲氧基苯甲醛 在 亚磷酸三乙酯 、 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 以64%的产率得到trans-2,3-dimethoxystilbene
  参考文献：
  名称：

  Quantification of the Resveratrol Analogs trans-2,3-Dimethoxy-stilbene and trans-3,4-Dimethoxystilbene in Rat Plasma: Application to Pre-Clinical Pharmacokinetic Studies

  摘要：

  反式-2,3-二甲氧基二苯乙烯（2,3-DMS）和反式-3,4-二甲氧基二苯乙烯（3,4-DMS）是两种合成的白藜芦醇（反式-3,5,4'-三羟基二苯乙烯）类似物。本研究开发并验证了一种简单的高效液相色谱法，用于测定大鼠血浆中的 2,3-DMS 和 3,4-DMS。该方法采用反相高效液相色谱柱，以乙腈和水的混合物为流动相，流速为 1.5 mL/min，梯度进样 12.5 分钟，分离温度为 50 ℃。定量下限为 10 纳克/毫升。验证成功后，随后在 Sprague-Dawley 大鼠体内研究了 2,3-DMS 和 3,4-DMS 的药代动力学特征。单次静脉给药（4 毫克/千克）后，2,3-DMS 在中心区的分布容积为中等（Vc = 2.71 ± 0.51 升/千克），清除速度相当快（Cl = 52.0 ± 7.0 毫升/分钟/千克），平均转运时间为中等（MTT0→last = 131.0 ± 4.5 分钟），但终末消除半衰期相当长（t1/2 λZ = 288.9 ± 92.9 分钟）。有趣的是，3,4-DMS 的药代动力学特征明显不同于 2,3-DMS，它的分布范围更广（Vc = 5.58 ± 1.73 升/千克），清除速度更快（Cl = 143.4 ± 40.5 毫升/分钟/千克），停留时间更短（MTT0→last = 61.4 ± 27.1 分钟）。单次口服（10 毫克/千克）后，2,3-DMS 的血浆暴露量低且不稳定（Cmax = 37.5 ± 23.7 纳克/毫升），口服生物利用度低（2.22% ± 2.13%），而 3,4-DMS 的口服生物利用度甚至比 2,3-DMS 更低。显然，甲氧基的位置对白藜芦醇类似物的药代动力学有重大影响。这项研究为今后设计白藜芦醇衍生物提供了有用的信息。

  DOI：

  10.3390/molecules19079577

文献信息

• Substituted CIS- and trans-stilbenes as therapeutic agents
  申请人：Vander Jagt David L.

  公开号：US20070249647A1

  公开（公告）日：2007-10-25

  The present invention relates to method(s) of treating a subject afflicted with cancer or a precancerous condition, an inflammatory disease or condition, and/or stroke or other ischemic disease or condition, the method comprising administering to the subject or patient in need a composition comprising a therapeutically effective amount of a substituted cis or trans-stilbene.

  本发明涉及治疗患有癌症或癌前病变、炎症性疾病或病情以及中风或其他缺血性疾病或病情的方法，该方法包括向需要的受试者或患者施用含有一定治疗有效量的取代的顺式或反式-芪的组合物。
• [EN] COSMETIC COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSITIONS COSMÉTIQUES ET PROCÉDÉS D'UTILISATION
  申请人：STC UNM

  公开号：WO2020112998A1

  公开（公告）日：2020-06-04

  The present invention relates to substituted stilbenes and dienones which exhibit unexpected dual activity, as inhibitors of NFKB and as agonists (activators) ofNrf2. In particular, these compounds show dual activity and it has been discovered that these compounds are particularly useful in the treatment of certain cosmetic applications and in rejuvenating and beautifying skin and other keratinous tissue of a subject in need. Cosmetic compositions and methods of using said compositions in combination with other components are disclosed herein.

  本发明涉及替代的stilbenes和dienones，表现出意外的双重活性，作为NFKB的抑制剂和Nrf2的激动剂。特别是，这些化合物展现了双重活性，已经发现这些化合物在治疗某些化妆品应用以及在使需要的主体的皮肤和其他角质组织恢复活力和美化方面特别有用。本文披露了化妆品组合物以及使用所述组合物与其他成分结合的方法。
• Activation of anti-oxidant Nrf2 signaling by substituted trans stilbenes
  作者：Lorraine M. Deck、Lisa J. Whalen、Lucy A. Hunsaker、Robert E. Royer、David L. Vander Jagt

  DOI：10.1016/j.bmc.2017.01.005

  日期：2017.2

  is the issue of selectivity. In the present study, substituted trans stilbenes were identified as activators of Nrf2. These activators of Nrf2 are not highly electrophilic and therefore are unlikely to activate Nrf2 through covalent modification of Keap1. Dose-response studies demonstrated that a range of substituents on either ring of the trans stilbenes, especially fluorine and methoxy substituents

  Nrf2是cap'n'collar转录因子家族的成员，是II期排毒和抗氧化基因以及抗炎和神经保护基因的主要调节剂。在许多慢性疾病中炎症和氧化应激的重要性支持了抗氧化剂Nrf2信号转导可能具有治疗潜力的概念。许多Nrf2激活剂已进入临床试验。Nrf2与它的结合伴侣Keap1结合存在于胞质溶胶中，Keap1是一种富含硫醇的氧化还原传感蛋白。响应于氧化和亲电子应力，Keap1的选定半胱氨酸残基被修饰，从而将Keap1锁定在Nrf2-Keap1复合物中，并使新合成的Nrf2进入细胞核。激活Nrf2的多种化学物质，包括多种天然产物，是亲电试剂，通常通过迈克尔加成来修饰Keap1，从而导致Nrf2激活。作为Keap1的亲电子共价修饰剂的Nrf2活化剂的设计，一个需要关注的问题是选择性问题。在本研究中，替代反式斯蒂芬苯酯被鉴定为Nrf2的激活剂。这些Nrf2激活剂不是高度亲电的，因此不太可能通过Keap
• Photochemistry of stilbenes. 8. Eliminative photocyclization of o-methoxystilbenes
  作者：Frank B. Mallory、M. Jonathan Rudolph、Soon M. Oh

  DOI：10.1021/jo00280a032

  日期：1989.9
• Substituted <i>trans</i>-Stilbenes, Including Analogues of the Natural Product Resveratrol, Inhibit the Human Tumor Necrosis Factor Alpha-Induced Activation of Transcription Factor Nuclear Factor KappaB
  作者：Justin J. Heynekamp、Waylon M. Weber、Lucy A. Hunsaker、Amanda M. Gonzales、Robert A. Orlando、Lorraine M. Deck、David L. Vander Jagt

  DOI：10.1021/jm060630x

  日期：2006.11.30

  The transcription factor nuclear factor kappaB (NF-kappa B), which regulates expression of numerous antiinflammatory genes as well as genes that promote development of the prosurvival, antiapoptotic state is up-regulated in many cancer cells. The natural product resveratrol, a polyphenolic trans-stilbene, has numerous biological activities and is a known inhibitor of activation of NF-kappa B, which may account for some of its biological activities. Resveratrol exhibits activity against a wide variety of cancer cells and has demonstrated activity as a cancer chemopreventive against all stages, i.e., initiation, promotion, and progression. The biological activities of resveratrol are often ascribed to its antioxidant activity. Both antioxidant activity and biological activities of analogues of resveratrol depend upon the number and location of the hydroxy groups. In the present study, phenolic analogues of resveratrol and a series of substituted trans-stilbenes without hydroxy groups were compared with resveratrol for their abilities to inhibit the human tumor necrosis factor alpha-induced (TNF-alpha) activation of NF-kappa B, using the Panomics NF-kappa B stable reporter cell line 293/NF-kappa B-luc. A series of 75 compounds was screened to identify substituted trans-stilbenes that were more active than resveratrol. Dose-response studies of the most active compounds were carried out to obtain IC50 values. Numerous compounds were identified that were more active than resveratrol, including compounds that were devoid of hydroxy groups and were 100-fold more potent than resveratrol. The substituted trans-stilbenes that were potent inhibitors of the activation of NF-kappa B generally did not exhibit antioxidant activity. The results from screening were confirmed using BV-2 microglial cells where resveratrol and analogues were shown to inhibit LPS-induced COX-2 expression.