(E)-3-(thiophen-2-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one | 127034-43-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-3-(thiophen-2-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 英文别名: (E)-3-(2-thienyl)-1-(3,4,5-trimethoxyphenyl)-3-phenylprop-2-en-1-one；(E)-3-thiophen-2-yl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 127034-43-9
• 化学式: C₁₆H₁₆O₄S
• 分子量: 304.367
• InChiKey: BWGAMTYKVBCHPG-VOTSOKGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  73
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzylpentacarbonylmanganese 、 (E)-3-(thiophen-2-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 以 petroleum ether 为溶剂， 以57%的产率得到[[1-(2-thienyl)-2-(3,4,5-trimethoxyphenyl)carbonyl-κO]ethenyl-κC(1)]tetracarbonylmanganese
  参考文献：
  名称：

  Preparation of cyclomanganated chalcones and their reactions with methyl acrylate and other α, β-unsaturated carbonyl compounds

  摘要：

  Chalcones [(E)-1,3-diarylprop-2-en-1-ones] react with benzyltetracarbonylmanganese under reflux in petroleum spirit to give two types of cyclomanganation products. The first, involving metallation at the alkenyl beta-carbon of the enone, are derivatives of [[1-phenyl-2-phenylcarbonyl-kappa O]ethenyl-kappa C-1]tetracarbonylmanganese, while the second type, manganated at the aryl ring ortho-carbon, are derivatives of [2-[3-phenylprop-2-en-1-onyl-kappa O]phenyl-kappa C-1]tetracarbonylmangane In general, more ''alkene-manganated'' than ''ring-manganated'' product is formed, with the ratio influenced significantly by certain substituents, e.g. a 4-CF3 substituent on the phenyl ring at C3 of the enone strongly promotes ''alkene-manganation''. in some cases there are minor by-products derived from coupling of two chalcone molecules after initial cyclomanganation. The crystal structures are reported for two such products, [2-((1S*,2R*,3S*)-1-hydroxy-1-((E)-2-(2-trifluoromethylphenyl)ethenyl)-3-(2-trifluoromethylphenyl)-6-methoxy-2-indanylcarbonyl- kappa O)-6-methoxyphenyl-kappa C-1]tetracarbonylmanganese and (1S*,4S*,5R*)-5-(4-bromobenzoyl)-1-(4-bromophenyl)-3,4-di-(4-trifluoromethylphenyl)cyclopent-2-en-1-ol.In acetonitrile under reflux, alkene-manganated chalcones react with methyl acrylate (methyl propenoate) to form derivatives of methyl (E)-4,6-diphenyl-6-oxohex-2-enoate and of 5-(2-methoxycarbonylethyl)-3,5-diphenylfuran-2-(5H)-one. The latter butenolides are not formed when the reactions are carried out in carbon tetrachloride, only the former alpha,beta-unsaturated esters. By contrast, in a few reactions studied, acrolein (propenal) and methyl vinyl ketone (but-3-en-2-one) give only the butenolide products when treated with alkene-manganated chalcones in refluxing acetonitrile. An exception is the reaction of methyl vinyl ketone with [[1 -(3,4,5-trimethoxyphenyl)-2-(4-chlorophenylcarbonyl-kappa O)]ethenyl-kappa C-1]tetracarbonylmanganese to form the cyclized product 5-acetyl-1-(4-chlorophenyl)3-(3,4,5-trimethoxyphenyl)cyclopent-2-en-1-ol.

  DOI：

  10.1016/0022-328x(95)05488-b
• 作为产物：
  描述：

  2-噻吩甲醛 、 3',4',5'-三甲氧基苯乙酮 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以84%的产率得到(E)-3-(thiophen-2-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  3,4-乙撑二氧基硫代苯基-2-丙-1-酮类似物的体外细胞毒性谱的不同合成和评价。

  摘要：

  通过缩合反应制备了一系列新的3,4-亚乙基二氧噻吩（EDOT）附加的丙烯酮，并评估了它们对五种人类癌细胞系的体外细胞毒性作用。还建立了EDOT掺入的2-丙烯酮衍生物的初步构效关系。EDOT附加的烯酮对人癌细胞具有明显的细胞毒性。活性最高的类似物（E）-3-（2,3-二氢噻吩并[3,4- b ] [1,4]二恶英-5-基）-1-（3,4,5-三甲氧基苯基）prop-2 ‐en ‐‐‐‐‐‐‐‐‐‐‐‐‐（3 p，GI 50 = 110 n m），严重抑制了癌细胞的克隆潜力，并诱导了G2 / M期的细胞周期停滞，并导致HCT116结肠癌细胞具有> 4 N DNA含量的积累。此外，3 p表现出对人类拓扑异构酶I的酶活性的弱抑制作用。分子对接研究表明，该化合物优先结合至人类检查点2激酶（Chk2）催化域的ATP结合口袋，从而鉴定出新的二芳基2丙烯酮化学型可开发有效的Chk2抑制剂。

  DOI：

  10.1002/cmdc.201900225

文献信息

• [EN] 2,3,5 TRISUBSTITUTED PYRROLE DERIVATIVES AS TOPOISOMERASE INHIBITORS AND THERAPEUTIC USES THEREOF<br/>[FR] DÉRIVÉS TRISUBSTITUÉS 2, 3, 5 DE PYRROLE EN TANT QU'INHIBITEURS DE TOPOISOMÉRASE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：UNIV OF MYSORE

  公开号：WO2017029684A1

  公开（公告）日：2017-02-23

  The compounds of Formula (1) having topoisomerase inhibitory effect includes [Formula should be inserted here] wherein, R1 is selected from a group consisting of H, OR5, optionally substituted C1-C12 alkyl, haloalkyl, C2-C12alkenyl, C2-C12alkynyl, C1-C12alkyloxy, C1-C12haloalkyloxy, C2-C10 heteroalkyl, C3- C12 cycloalkyl, C3-C12cycloalkenyl, C2- C12heterocycloalkyl, C2-C2 heterocycloalkenyl, C6-C18aryl, and C1-C18heteroaryl; R2, R3 and R4 are independently selected from a group consisting of H, halogen, CN, - NO2, SH, CF3, OH, CO2H, CONH2, OCF3, optionally substituted C1-C12alkyl, optionally substituted C1-C12haloalkyl optionally substituted C2-C12alkenyl, optionally substituted C2- C12alkynyl, optionally substituted C1-C12alkyloxy, optionally substituted C1- C12haloalkyloxy, optionally substituted C2-C12heteroalkyl, optionally substituted C3- C12cycloalkyl, optionally substituted C3-C12 cycloalkenyl, optionally substituted C2-C12 heterocycloalkyl, optionally substituted C2-C12 heterocycloalkenyl, optionally substituted C6- C18aryl, and optionally substituted C1-C18heteroaryl; R5 is selected H, optionally substituted C1-C12alkyl, optionally substituted C2- C12alkenyl, optionally substituted optionally substituted C1-C12 haloalkyl, optionally substituted C3-C12cycloalkyl, optionally substituted C6- C18aryl, and optionally substituted C1- Ci18heteroaryl; or a pharmaceutically acceptable salt, N-oxide, or prodrug thereof.

  具有拓扑异构酶抑制作用的Formula（1）化合物包括[在此插入公式]其中，R1从以下组中选择：H，OR5，可选择取代的C1-C12烷基，卤代烷基，C2-C12烯基，C2-C12炔基，C1-C12烷氧基，C1-C12卤代烷氧基，C2-C10杂基烷基，C3-C12环烷基，C3-C12环烯基，C2-C12杂环烷基，C2-C2杂环烯基，C6-C18芳基和C1-C18杂芳基；R2、R3和R4分别从以下组中选择：H，卤素，CN，-NO2，SH，CF3，OH，CO2H，CONH2，OCF3，可选择取代的C1-C12烷基，可选择取代的C1-C12卤代烷基，可选择取代的C2-C12烯基，可选择取代的C2-C12炔基，可选择取代的C1-C12烷氧基，可选择取代的C1-C12卤代烷氧基，可选择取代的C2-C12杂基烷基，可选择取代的C3-C12环烷基，可选择取代的C3-C12环烯基，可选择取代的C2-C12杂环烷基，可选择取代的C2-C12杂环烯基，可选择取代的C6-C18芳基，可选择取代的C1-C18杂芳基；R5选择为H，可选择取代的C1-C12烷基，可选择取代的C2-C12烯基，可选择取代的可选择取代的C1-C12卤代烷基，可选择取代的C3-C12环烷基，可选择取代的C6-C18芳基，可选择取代的C1-Ci18杂芳基；或其药学上可接受的盐、N-氧化物或前药。
• Divergent Synthesis and Evaluation of the in vitro Cytotoxicity Profiles of 3,4‐Ethylenedioxythiophenyl‐2‐propen‐1‐one Analogues
  作者：Jayachandran Karunakaran、Nachiappan Dhatchana Moorthy、Somenath Roy Chowdhury、Saleem Iqbal、Hemanta K. Majumder、Krishnasamy Gunasekaran、Elangovan Vellaichamy、Arasambattu K. Mohanakrishnan

  DOI：10.1002/cmdc.201900225

  日期：2019.8.6

  five human cancer cell lines. Preliminary structure–activity relationships of EDOT‐incorporated 2‐propenone derivatives were also established. The EDOT‐appended enones demonstrated significant cytotoxicity against human cancer cell lines. The most active analogue, (E)‐3‐(2,3‐dihydrothieno[3,4‐b][1,4]dioxin‐5‐yl)‐1‐(3,4,5‐trimethoxyphenyl)prop‐2‐en‐1‐one (3 p, GI50=110 nm), severely inhibited the clonogenic

  通过缩合反应制备了一系列新的3,4-亚乙基二氧噻吩（EDOT）附加的丙烯酮，并评估了它们对五种人类癌细胞系的体外细胞毒性作用。还建立了EDOT掺入的2-丙烯酮衍生物的初步构效关系。EDOT附加的烯酮对人癌细胞具有明显的细胞毒性。活性最高的类似物（E）-3-（2,3-二氢噻吩并[3,4- b ] [1,4]二恶英-5-基）-1-（3,4,5-三甲氧基苯基）prop-2 ‐en ‐‐‐‐‐‐‐‐‐‐‐‐‐（3 p，GI 50 = 110 n m），严重抑制了癌细胞的克隆潜力，并诱导了G2 / M期的细胞周期停滞，并导致HCT116结肠癌细胞具有> 4 N DNA含量的积累。此外，3 p表现出对人类拓扑异构酶I的酶活性的弱抑制作用。分子对接研究表明，该化合物优先结合至人类检查点2激酶（Chk2）催化域的ATP结合口袋，从而鉴定出新的二芳基2丙烯酮化学型可开发有效的Chk2抑制剂。
• MODIFIED CHALCONE COMPOUNDS AS ANTIMITOTIC AGENTS
  申请人：ROSE Seth D.

  公开号：US20070265317A1

  公开（公告）日：2007-11-15

  Antimitotic agents comprising a modified chalcone or modified chalcone derivative are disclosed. The modified chalcone or modified chalcone derivative compounds are of the general formula CHAL-LIN—COV, wherein CHAL is a chalcone or chalcone derivative portion, LIN is an optional linker portion, and COV is a covalent bonding portion (e.g., an α,β-unsaturated thiol ester group). The modified chalcone or modified chalcone derivative compounds provide an improved method of interference with tubulin polymerization, for example by covalent (and essentially irreversible) bonding between tubulin and the covalent bonding portion, potentially resulting in a decrease in tumor size and/or disappearance of the cancer, to the benefit of cancer patients.

  本发明涉及一种包含改性查尔酮或改性查尔酮衍生物的抗有丝分裂剂。改性查尔酮或改性查尔酮衍生物化合物的一般式为CHAL-LIN-COV，其中，CHAL是查尔酮或查尔酮衍生物部分，LIN是可选的连接部分，COV是共价键合部分（例如α，β-不饱和硫酯酯基）。改性查尔酮或改性查尔酮衍生物化合物提供了一种改进的干扰微管聚合的方法，例如通过微管和共价键合部分之间的共价键合（基本上是不可逆的），可能导致肿瘤大小减小和/或癌症消失，从而使癌症患者受益。
• Chalcones: a new class of antimitotic agents
  作者：Michael L. Edwards、David M. Stemerick、Prasad S. Sunkara

  DOI：10.1021/jm00169a021

  日期：1990.7

  A series of chalcones was evaluated as antimitotic agents. One of these, (E)-1-(2,5-dimethoxyphenyl)-3-[4-(dimethylamino)phenyl]-2-methyl-2-pr open- 1-one) (73), was found to be an effective antimitotic agent at a concentration of 4 nM in an in vitro HeLa cell test system. When evaluated in experimental tumor models in vivo, this compound exhibited antitumor activity against L1210 leukemia and B16 melanoma.
• Synthetic compounds from an <i>in house</i> library as inhibitors of falcipain-2 from <i>Plasmodium falciparum</i>
  作者：Jean Borges Bertoldo、Louise Domeneghini Chiaradia-Delatorre、Alessandra Mascarello、Paulo César Leal、Marlon Norberto Sechini Cordeiro、Ricardo José Nunes、Emir Salas Sarduy、Philip Jon Rosenthal、Hernán Terenzi

  DOI：10.3109/14756366.2014.920839

  日期：2015.3.4

  Falcipain-2 (FP-2) is a key cysteine protease from the malaria parasite Plasmodium falciparum. Many previous studies have identified FP-2 inhibitors; however, none has yet met the criteria for an antimalarial drug candidate. In this work, we assayed an in-house library of non-peptidic organic compounds, including (E)-chalcones, (E)-N'-benzylidene-benzohydrazides and alkylesters of gallic acid, and assessed the activity toward FP-2 and their mechanisms of inhibition. The (E)-chalcones 48, 54 and 66 showed the lowest IC50 values (8.5 +/- 0.8 mu M, 9.5 +/- 0.2 mu M and 4.9 +/- 1.3 mu M, respectively). The best inhibitor (compound 66) demonstrated non-competitive inhibition, and using mass spectrometry and fluorescence spectroscopy assays, we suggest a potential allosteric site for the interaction of this compound, located between the catalytic site and the hemoglobin binding arm in FP-2. We combined structural biology tools and mass spectrometry to characterize the inhibition mechanisms of novel compounds targeting FP-2.