3-(3,4,5-trimethoxyphenyl)propiolic acid | 4698-21-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(3,4,5-trimethoxyphenyl)propiolic acid
• 英文别名: 3-(3,4,5-trimethoxyphenyl)-2-propynoic acid；3-(3,4,5-trimethoxyphenyl)propynoic acid；(3,4,5-Trimethoxyphenyl)propiolic acid；3,4,5-trimethoxyphenylpropiolic acid；3,4,5-Trimethoxypropiolic acid；<3,4,5-Trimethoxy-phenyl>-propiolsaeure；3-(3,4,5-Trimethoxyphenyl)prop-2-ynoic acid
• CAS: 4698-21-9
• 化学式: C₁₂H₁₂O₅
• 分子量: 236.224
• InChiKey: JCJHIQYGYVUQEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  3-(3,4,5-trimethoxyphenyl)propiolic acid 在 titanium(IV) isopropylate 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 trans/cis-3-(3,4,5-trimethoxyphenyl)propiolic acid 4-(4-hydroxycyclohexylamino)cyclohexyl ester
  参考文献：
  名称：

  New structure–activity relationship studies in a series of N,N-bis(cyclohexanol)amine aryl esters as potent reversers of P-glycoprotein-mediated multidrug resistance (MDR)

  摘要：

  As a continuation of previous research on a new series of potent and efficacious P-gp-dependent multidrug resistant (MDR) reversers with a N,N-bis(cyclohexanol) amine scaffold, we have designed and synthesized several analogs by modulation of the two aromatic moieties linked through ester functions to the N,N-bis(cyclohexanol) amine, aiming to optimize activity and to extend structure-activity relationships (SAR) within the series. This scaffold, when esterified with two different aromatic carboxylic acids, gives origin to four geometric isomers (cis/trans, trans/trans, cis/cis and trans/cis).The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Most of them resulted in being potent modulators of the extrusion pump P-gp, showing potency values ([I](0.5)) in the submicromolar and nanomolar range. Of these, compounds 2b, 2c, 3d, 5a-d and 6d, showed excellent efficacy with a alpha(max) close to 1. Selected compounds (2d, 3a, 3b, 5a-d) were further studied to evaluate their doxorubicin cytotoxicity potentiation (RF) on doxorubicin-resistant erythroleukemia K562 cells and were found able to enhance significantly doxorubicin cytotoxicity on K562/DOX cells.The results of both pirarubicin uptake and the cytotoxicity assay, indicate that the new compounds of the series are potent P-gp-mediated MDR reversers. They present a structure with a mix of flexible and rigid moieties, a property that seems critical to allow the molecules to choose the most productive of the several binding modes possible in the transporter recognition site.In particular, compounds 5c and 5d, similar to the already reported analogous isomers 1c and 1d,(29) are potent and efficacious modulators of P-gp-dependent MDR and may be promising leads for the development of MDR-reversal drugs. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.019
• 作为产物：
  描述：

  3,4,5-三甲基肉桂酸甲酯 在 氢氧化钾 、 溴 作用下， 以 乙醇 、 氯仿 为溶剂， 生成 3-(3,4,5-trimethoxyphenyl)propiolic acid
  参考文献：
  名称：

  某些二烯和烯酸酯的合成和光谱研究

  摘要：

  所述的二烯酯的合成反式-cinnamyl失败者肉桂酸酯和反式-cinnamyl顺-肉桂酸酯类型和的enynic酯反式-cinnamyl苯基丙和phenylpropargyl反式-肉桂酸酯类型进行说明。记录了特征性的UV，IR和NMR吸收带。

  DOI：

  10.1016/s0040-4020(01)98419-4

文献信息

• Palladium-catalyzed decarboxylative aminocarbonylation with alkynoic acid and tertiary amine for the synthesis of alkynyl amide
  作者：Muhammad Aliyu Idris、Myungjin Kim、Jeung Gon Kim、Sunwoo Lee

  DOI：10.1016/j.tet.2019.04.030

  日期：2019.8

  We developed a method for the synthesis of alkynyl amides via the carbonylation of alkynoic acids and C-N activation of tertiary amines. The reaction of alkynoic acid and tertiary amine with carbon monoxide using a palladium catalyst in the presence of oxygen, KI, and K3PO4, gave the desired alkynyl amides in good yields.

  我们开发了一种通过炔酸的羰基化和叔胺的CN活化合成炔基酰胺的方法。在氧，KI和K 3 PO 4的存在下，使用钯催化剂使炔酸和叔胺与一氧化碳反应，以良好的收率得到所需的炔基酰胺。
• Cyclic amide compound
  申请人：KOWA CO., LTD.

  公开号：US20030096828A1

  公开（公告）日：2003-05-22

  The invention relates to compounds represented by the following general formula (1): 1 wherein A is an aromatic compound which may be substituted, or the like, B is a nitrogen atom or CH, X is a lower alkylene group which may be substituted, or the like, Yi s a single bond or the like; Z is a divalent residue of benzene which may be substituted, or the like, and m and n are independently an integer of 1 to 4, and medicines comprising such a compound. These compounds have an excellent inhibitory effect on the production of an IgE antibody and are hence useful as antiallergic agents and the like.

  该发明涉及由以下一般式（1）表示的化合物： 1 其中A是可能被取代的芳香化合物，B是氮原子或CH等，X是可能被取代的较低烷基基团，Y是单键等；Z是可能被取代的苯的二价残基，m和n分别是1到4的整数，以及包含这种化合物的药物。这些化合物对IgE抗体的产生具有出色的抑制作用，因此可用作抗过敏药物等。
• Palladium-Catalyzed Decarboxylative Trifluoroethylation of Aryl Alkynyl Carboxylic Acids
  作者：Jinil Hwang、Kyungho Park、Juseok Choe、Hongkeun Min、Kwang Ho Song、Sunwoo Lee

  DOI：10.1021/jo5003032

  日期：2014.4.4

  A trifluoroethylation of alkynes through a palladium-catalyzed decarboxylative coupling reaction was developed. When alkynyl carboxylic acids and ICH2CF3 were allowed to react with [Pd(η3-allyl)Cl]2/XantPhos and Cs2CO3 in N,N-dimethylformamide (DMF) at 80 °C for 1 h, the desired products were formed in good yields. This catalytic system showed high functional group tolerance.

  通过钯催化的脱羧偶联反应，开发了炔烃的三氟乙基化反应。当炔基羧酸和ICH 2 CF 3被允许通过[加入Pd（η反应3 -烯丙基）CL] 2 / XANTPHOS和Cs 2 CO 3在Ñ，Ñ在80二甲基甲酰胺（DMF）℃下反应1个小时后，将所需产物以高收率形成。该催化体系显示出高的官能团耐受性。
• Palladium-catalyzed decarboxylative coupling reaction with alkynyl carboxylic acids and arylsiloxanes
  作者：Jisun Jang、Gabriel Charles Edwin Raja、Ju-Hyeon Lee、Yujeong Son、Jimin Kim、Sunwoo Lee

  DOI：10.1016/j.tetlet.2016.08.095

  日期：2016.10

  A decarboxylative coupling reaction for alkynyl carboxylic acids and arylsiloxanes was developed using a palladium catalyst. This method provided the desired coupled products in moderate to good yields by reacting the alkynyl carboxylic acids and arylsiloxanes with Pd(dba)2 (1.0 mol %), 1,1-bis(diphenylphosphino)methane (1.0 mol %), and AgF2 (2.0 equiv) at 60 °C for 6 h.

  使用钯催化剂开发了炔基羧酸和芳基硅氧烷的脱羧偶联反应。通过使炔基羧酸和芳基硅氧烷与Pd（dba）2（1.0 mol％），1,1-双（二苯基膦基）甲烷（1.0 mol％）和AgF 2反应，该方法以中等至良好的产率提供了所需的偶联产物。（2.0当量）在60°C下放置6小时。
• Synthesis of tetrahydrofurocarbazolones via intramolecular Diels-Alder reactions
  作者：Jose S. Madalengoitia、Timothy L. Macdonald

  DOI：10.1016/s0040-4039(00)73719-1

  日期：1993.9

  10-Aryl-3a,4,10,10a-tetrahydrofuro[3,4-b]carbazol-1-ones were synthesized by an intramolecular Diels-Alder reaction. Exo/endo product ratios were found to be sensitive to both solvent and temperature. The synthesis of isoelliptitoxin 2, a hybrid molecule of ellipticine and 4'-demethylpodophyllotoxin, is presented.

  通过分子内Diels-Alder反应合成了10-芳基-3a，4,10,10a-四氢呋喃[3,4-b]咔唑-1-酮。发现外/内产物的比率对溶剂和温度均敏感。介绍了玫瑰树碱和4'-去甲基鬼臼毒素的杂合分子异椭圆毒素2的合成。