2-(3,5-二甲氧基苯氧基)乙酸 | 19728-23-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(3,5-二甲氧基苯氧基)乙酸
• 英文名称: 2-(3,5-dimethoxyphenoxy)acetic acid
• 英文别名: (3,5-dimethoxyphenoxy)acetic acid；3,5-dimethoxyphenoxyacetic acid；<3,5-Dimethoxy-phenoxy>-essigsaeure；3,5-Dimethoxy-phenoxyessigsaeure；3,5-Dimethoxyphenoxy-essigsaeure；(3,5-Dimethoxy-phenoxy)acetic acid
• CAS: 19728-23-5
• 化学式: C₁₀H₁₂O₅
• mdl: MFCD09049678
• 分子量: 212.202
• InChiKey: AELFBZMVKKOCQJ-UHFFFAOYSA-N

物化性质

• 熔点：
  145.5-146.5 °C(Solv: water (7732-18-5))
• 沸点：
  374.7±27.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3,5-二甲氧基苯氧基)乙酸 在 lithium hydroxide 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 rac-(SR)-{(5SR)-8-methoxy-1-methyl-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-5-yl}-(3,5-dimethoxyphenoxy)acetic acid
  参考文献：
  名称：

  Novel Benzo[1,4]diazepin-2-one Derivatives as Endothelin Receptor Antagonists

  摘要：

  Since its discovery in 1988 by Yanagisawa et al., endothelin (ET), a potent vasoconstrictor, has been widely implicated in the pathophysiology of cardiovascular, cerebrovascular, and renal diseases. Many research groups have embarked on the discovery and development of ET receptor antagonists for the treatment of such diseases. While several compounds, e.g., ambrisentan 2, are in late clinical trials for various indications, one compound (bosentan, Tracleer) is being marketed to treat pulmonary arterial hypertension. Inspired by the structure of ambrisentan 2, we designed a novel class of ET receptor antagonists based on a 1,3,4,5-tetrahydro-1H-benzo[e] [1,4]diazepin-2-one scaffold. Here, we report on the preparation as well as the in vitro and in vivo structure-activity relationships of these derivatives. Potent dual ETA/ETB receptor antagonists with affinities in the low nanomolar range have been identified. In addition, several compounds efficiently reduced arterial blood pressure after oral administration to Dahl salt sensitive rats. In this animal model, the efficacy of the benzo [e] [1,4] diazepin-2-one derivative rac-39au was superior to that of racemic ambrisentan, rac-2.

  DOI：

  10.1021/jm031115r
• 作为产物：
  描述：

  2-(3,5-二甲氧基苯氧基)乙酸乙酯 在 sodium hydroxide 、 水 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 2-(3,5-二甲氧基苯氧基)乙酸
  参考文献：
  名称：

  Synthesis and Insect Antifeedant Activity of Aurones against Spodoptera litura Larvae

  摘要：

  A series of aurones were prepared from various phenols via phenoxy acetic acids and coumaranones and evaluated for insect antifeedant activity against the common cutworm (Spodoptera litura). The naturally occurring aurone was most active at an ED50 of 0.12 mu mol/cm(2). The synthetic precursor, coumaranones, showed that the introduction of methoxyl and methyl groups to the benzene ring increased insect antifeedant activity. Similarly, the tested aurones showed that the introduction of methoxyl group to the A and/or B rings increased the insect antifeedant activity, but 4,5,6- and 3',4',5'-trisubstituted compounds did not show this activity in this test. The hydroxylation of aurones in the B ring should be disadvantageous for insect antifeedant activity against S. litura. Although the melting points did not correlate well with the insect antifeedant activity, compounds that were nearly inactive had high melting points. A significant correlation was noted between biological activity (pED(50)) and a hydrogen-bonding parameter calculated from the R-f value obtained from SiOH thin-layer chromatography and a lipophilicity parameter (log k) calculated from the retention time in ODS high-performance liquid chromatography. The respective correlation coefficients (r) were -0.83 and -0.70. The introduction of alkoxy and alkyl groups along with adequate hydrogen bonding seems to contribute to the antifeedant activity of the compounds tested.

  DOI：

  10.1021/jf062562t

文献信息

• Catalyst-Free Photoredox Addition-Cyclisations: Exploitation of Natural Synergy between Aryl Acetic Acids and Maleimide
  作者：David W. Manley、Andrew Mills、Christopher O'Rourke、Alexandra M. Z. Slawin、John C. Walton

  DOI：10.1002/chem.201304929

  日期：2014.4.25

  Suitably functionalised carboxylic acids undergo a previously unknown photoredox reaction when irradiated with UVA in the presence of maleimide. Maleimide was found to synergistically act as a radical generating photoxidant and as a radical acceptor, negating the need for an extrinsic photoredox catalyst. Modest to excellent yields of the product chromenopyrroledione, thiochromenopyrroledione and

  当在马来酰亚胺存在下用 UVA 照射时，适当官能化的羧酸会发生以前未知的光氧化还原反应。发现马来酰亚胺协同作用作为产生自由基的光氧化剂和作为自由基受体，不需要外在的光氧化还原催化剂。在 13 次制备性光解中获得了中等至极好的产率的产物色基吡咯二酮、硫代色基吡咯二酮和吡咯并喹啉二酮衍生物。原位核磁共振光谱用于研究每个反应。监测反应物衰变和产物堆积，从而绘制反应曲线。一种似是而非的机制，即光激发的马来酰亚胺充当氧化剂以产生自由基离子对，已被假设并得到 UV/Vis 的支持。光谱和 DFT 计算。
• Design, synthesis, and testing of potential antisickling agents. 4. Structure-activity relationships of benzyloxy and phenoxy acids
  作者：D. J. Abraham、P. E. Kennedy、A. S. Mehanna、D. C. Patwa、F. L. Williams

  DOI：10.1021/jm00374a006

  日期：1984.8

  small molecules, benzyloxy and phenoxy acids, as potent inhibitors of hemoglobin S (HbS) gelation. Structural modifications with a large number of each class confirm our earlier work that the highest activity is observed with compounds that contain dihalogenated aromatic rings with attached polar side chains. We have also found a halogenated aromatic malonic acid derivative to be quite active. Compounds

  在本文中，我们进一步确立了两类小分子，即苄氧基和苯氧基酸的活性，它们是血红蛋白S（HbS）凝胶化的有效抑制剂。每个类别都有大量结构修饰，这证实了我们较早的工作，即发现含有带有连接的极性侧链的二卤代芳环的化合物具有最高的活性。我们还发现卤代芳族丙二酸衍生物非常活泼。将本文报道的化合物与我们实验室研究的其他抗胶凝剂进行了比较。关于四种衍生物的抗胶凝活性和结合位点及其对血红蛋白（Hb）功能的变构机制的影响进行了评论。
• Photoassisted Synthesis of Complex Molecular Architectures: Dearomatization of Benzenoid Arenes with Aza-<i>o</i>-xylylenes via an Unprecedented [2+4] Reaction Topology
  作者：Dmitry M. Kuznetsov、Olga A. Mukhina、Andrei G. Kutateladze

  DOI：10.1002/anie.201602288

  日期：2016.6.6

  A new method was developed for the photoinduced dearomatization of arenes through an intramolecular cycloaddition with aza‐o‐xylylenes generated by excited‐state intramolecular proton transfer (ESIPT) in the readily available photoprecursors. The [2+4] topology of this cycloaddition is unprecedented for photo‐dearomatizations of benzenoid aromatic carbocycles. It provides rapid access to novel heterocycles

  一种新方法是通过对芳烃的光致脱芳构化开发的分子内环加成与氮杂Ó通过在容易获得的photoprecursors激发态分子内质子转移（ESIPT）产生-xylylenes。这种环加成反应的[2 + 4]拓扑结构对于苯型芳香族碳环化合物的光脱芳香化作用是前所未有的。它提供了快速获取新型杂环，即环己二烯基-恶唑烷醇-喹啉醇的能力，它们是广泛的光化学后转化的有价值的合成子。
• Dimethoxyaurones: Potent inhibitors of ABCG2 (breast cancer resistance protein)
  作者：Hong-May Sim、Chong-Yew Lee、Pui Lai Rachel Ee、Mei-Lin Go

  DOI：10.1016/j.ejps.2008.07.008

  日期：2008.11

  their ability to modulate ABCG2 (breast cancer resistance protein)-mediated multidrug resistance in vitro. Several members (0.5 microM) increased the accumulation of mitoxantrone (MX) in human breast cancer cells (MDA-MB-231) transfected with ABCG2 and re-sensitized these cells to the cytotoxic effects of MX. In the re-sensitization assay, aurones at 0.5 microM reduced the resistance of the transfected

  通过将4，6-二甲氧基苯并呋喃-3（2H）-1与各种苯甲醛在碱催化的醛醇缩合反应中反应，合成了一系列4,6-二甲氧基金错误。根据光谱和晶体学数据将AZ构型分配给了光环。测试了金黄色素在体外调节ABCG2（乳腺癌抗性蛋白）介导的多药抗性的能力。几个成员（0.5 microM）增加了用ABCG2转染的人乳腺癌细胞（MDA-MB-231）中米托蒽醌（MX）的积累，并使这些细胞对MX的细胞毒性作用重新敏感。在再敏化试验中，0.5 microM的金黄色素使转染细胞对MX的抗性降至亲代细胞的两倍，超过在相同浓度下测试的泛黄霉素C（FTC）。金黄色素（10 microM）还增加了钙黄绿素-AM在用ABCB1（P-糖蛋白）转染的MDCKII / MDR1细胞中的蓄积，其水平与在相同浓度下测试的维拉帕米相当。结构活性分析表明，对于ABCG2抑制作用，金质模板中亚苄基环B的取代作用不那么重要，对于具有未取代环
• Novel benzo-fused heterocycles as endothelin antagonisits
  申请人：Bolli Martin

  公开号：US20050124605A1

  公开（公告）日：2005-06-09

  The invention relates to novel benzo-fused heterocycles and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

  本发明涉及新型苯并杂环化合物及其用作制备药物组成物的活性成分。本发明还涉及相关方面，包括制备化合物的过程，含有其中一种或多种化合物的药物组成物，特别是它们作为内皮素受体拮抗剂的用途。