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(E)-1-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-one | 1056445-12-5

中文名称
——
中文别名
——
英文名称
(E)-1-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-one
英文别名
(E)-1-(3,4-dimethoxy-phenyl)-3-(4-fluoro-phenyl)propenone;(2E)-1-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-one
(E)-1-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-one化学式
CAS
1056445-12-5
化学式
C17H15FO3
mdl
——
分子量
286.303
InChiKey
QTKUEXSSQYRHHA-WEVVVXLNSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    3.7
  • 重原子数:
    21
  • 可旋转键数:
    5
  • 环数:
    2.0
  • sp3杂化的碳原子比例:
    0.12
  • 拓扑面积:
    35.5
  • 氢给体数:
    0
  • 氢受体数:
    4

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量

反应信息

  • 作为反应物:
    描述:
    (E)-1-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-oneplatinum(IV) oxide 氢气 作用下, 以 二氯甲烷乙酸乙酯 为溶剂, 20.0 ℃ 、101.33 kPa 条件下, 反应 1.0h, 以81%的产率得到1-(3,4-dimethoxy-phenyl)-3-(4-fluoro-phenyl)-propan-1-one
    参考文献:
    名称:
    AMINOAMIDES AS OREXIN ANTAGONISTS
    摘要:
    本发明涉及具有以下结构的化合物(I)其中Ar1,Ar2,Ar3,n和R1至R8的定义如本文所述,并且涉及其药用适宜的酸加盐、光学纯对映体、混合物或二对映异构体。这些化合物是促进睡眠的受体拮抗剂,可能在涉及促进睡眠途径的疾病治疗中有用,如睡眠障碍。
    公开号:
    US20080221166A1
  • 作为产物:
    描述:
    对氟苯甲醛3,4-二甲氧基苯乙酮 在 potassium hydroxide 作用下, 以 乙醇 为溶剂, 以78%的产率得到(E)-1-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-one
    参考文献:
    名称:
    Design, Synthesis, Characterization and In Silico Molecular Docking Studies and In Vivo Anti-inflammatory Activity of Pyrazoline Clubbed Thiazolinone Derivatives
    摘要:
    吡唑啉类化合物在其对高锰酸盐和新生氢的反应中表现出与不饱和化合物相似的行为,类似于脂肪衍生物。这种核与各种生物活性有关,包括炎症作用。噻唑酮是一种含有硫和氮原子以及羰基的杂环化合物。由于其多种生物活性,如抗炎、抗微生物、抗增殖、抗病毒、抗抽搐等,噻唑酮及其衍生物一直受到持续关注。研究的目的是将吡唑啉核与噻唑酮结合,以获得显著的抗炎活性。合成的化合物在化学上被表征以确定其化学结构,并评估其作为抗炎药物的效果。 在本研究中,通过三步反应合成了八种取代吡唑啉衍生物(PT1-PT8)。这些化合物经过红外、质谱和核磁共振光谱以及元素分析数据的光谱分析。所有合成的衍生物均评估了它们的体内抗炎活性。通过使用吲哚美辛作为参考化合物,评估了合成衍生物对COX-1和COX-2的亲和力,通过AutoDock Vina进行分子对接可视化。 化合物PT-1、PT-3、PT-4和PT-8在第3小时表现出显著的抗炎活性,分别为50.7%、54.3%、52.3%和57%,接近标准药物吲哚美辛(61.9%)的效果。从选定的抗炎靶点来看,合成的衍生物与COX-1和COX-2受体的相互作用更好,吲哚美辛的对接分数为-6.5 kJ/mol,化合物PT-1在COX-1上表现出最高的对接分数为-9.1 kJ/mol,而化合物PT-8在COX-2上的对接分数为9.4 kJ/mol。 结论是合成的衍生物与COX-2受体的相互作用比与COX-1受体的相互作用更多,因为与COX-2受体的对接分数非常好。可以得出结论,合成的衍生物(PT-1至PT-8)是有效的COX-2抑制剂。
    DOI:
    10.2174/1570178617999201106113114
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文献信息

  • A novel series of benzothiazepine derivatives as tubulin polymerization inhibitors with anti-tumor potency
    作者:Bin Wang、Li-Ren Wang、Lu-Lu Liu、Wei Wang、Ruo-Jun Man、Da-Jun Zheng、Yu-Shan Deng、Yu-Shun Yang、Chen Xu、Hai-Liang Zhu
    DOI:10.1016/j.bioorg.2020.104585
    日期:2021.3
    In this work, a series of diaryl benzo[b][1,4]thiazepine derivatives D1-D36 were synthesized and screened as tubulin polymerization inhibitors with anti-tumor potency. They were designed by introducing the seven-member ring benzothiazepine as the linker for CA-4 modification for the first time. Among them, the hit compound D8 showed potential on inhibiting the growth of several cancer cell lines (IC50
    在这项工作中,合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中,命中化合物D8显示出抑制多种癌细胞系生长的潜力(IC 50值:HeLa 1.48 μM,MCF-7 1.47 μM,HT29 1.52 μM 和 A549 1.94 μM),与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明,D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式,推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论,这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。
  • US7829563B2
    申请人:——
    公开号:US7829563B2
    公开(公告)日:2010-11-09
  • [EN] AMINOAMIDES AS OREXIN ANTAGONISTS<br/>[FR] AMINOAMIDES COMME ANTAGONISTES DE L'OREXINE
    申请人:HOFFMANN LA ROCHE
    公开号:WO2008107335A1
    公开(公告)日:2008-09-12
    [EN] The present invention relates to compounds of formula (I) wherein Ar1, Ar2 and Ar3 are independently from each other unsubstituted or substituted aryl or heteroaryl; R1, R2 and R3 are independently from each other hydroxy, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, 3-hydroxy-oxetan-3-yl, SO2 -lower alkyl or di-lower alkyl amino; R4 /R5 are independently from each other hydrogen, lower alkyl, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, -(CH2)o-O-lower alkyl, -(CH2)o-N-(lower alkyl)2, (CH2)p-cycloalkyl, (CH2)p-aryl, which aryl ring may be substituted by halogen, or R4 and R5 may form together with the N-atom to which they are attached a heterocyclic ring, optionally with further ring-heteroatoms selected from N, O or S; R6 is hydrogen or lower alkyl; R7 is hydrogen or lower alkyl; R8 is hydrogen or cyano; n is 0, 1, 2 or 3; o is 1, 2 or 3; p is 0, 1 or 2; or to pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixtures thereof. It has been found that the compounds of formula (I) are orexin receptor antagonists and the related compounds may be useful in the treatment of disorders, in which orexin pathways are involved like sleep disorders.
    [FR] La présente invention porte sur des composés de formule (I), dans laquelle Ar1, Ar2 et Ar3 représentent indépendamment les uns des autres aryle ou hétéroaryle substitué ou non substitué ; R1, R2 et R3 représentent indépendamment les uns des autres hydroxy, halogène, alkyle inférieur, alkyle inférieur substitué par halogène, alcoxy inférieur, alcoxy inférieur substitué par halogène, cyano, 3-hydroxy-oxétan-3-yle, SO2-alkyle inférieur ou di-alkyle inférieur amino ; R4/R5 représentent indépendamment l'un de l'autre hydrogène, alkyle inférieur, alkyle inférieur substitué par halogène, alkyle inférieur substitué par hydroxy, -(CH2)o-O-alkyle inférieur, -(CH2)o-N-(alkyle inférieur)2, (CH2)p-cycloalkyle, (CH2)p-aryle, lequel noyau aryle peut être substitué par halogène, ou R4 et R5 peuvent former, conjointement avec l'atome de N auquel ils sont attachés, un noyau hétérocyclique facultativement avec d'autres hétéroatomes de cycle choisis parmi N, O ou S ; R6 représente hydrogène ou alkyle inférieur ; R7 représente hydrogène ou alkyle inférieur ; R8 représente hydrogène ou cyano ; n vaut 0, 1, 2 ou 3 ; o vaut 1, 2 ou 3 ; p vaut 0, 1 ou 2 ; ou sur des sels d'addition avec les acides pharmaceutiquement appropriés, des énantiomères optiquement purs, des racémates ou mélanges diastéréoisomères de ceux-ci. Il a été découvert que les composés de formule (I) sont des antagonistes des récepteurs de l'orexine et les composés apparentés peuvent être utiles dans le traitement de troubles dans lesquels les voies de l'orexine sont mises en jeu, comme les troubles du sommeil.
  • AMINOAMIDES AS OREXIN ANTAGONISTS
    申请人:Gobbi Luca
    公开号:US20080221166A1
    公开(公告)日:2008-09-11
    The present invention relates to compounds of formula I wherein Ar 1 , Ar 2 , Ar 3 , n, and R 1 to R 8 are as defined herein and to pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixtures thereof. These compounds are orexin receptor antagonists and may be useful in the treatment of disorders, in which orexin pathways are involved, like sleep disorders.
    本发明涉及具有以下结构的化合物(I)其中Ar1,Ar2,Ar3,n和R1至R8的定义如本文所述,并且涉及其药用适宜的酸加盐、光学纯对映体、混合物或二对映异构体。这些化合物是促进睡眠的受体拮抗剂,可能在涉及促进睡眠途径的疾病治疗中有用,如睡眠障碍。
  • Design, Synthesis, Characterization and In Silico Molecular Docking Studies and In Vivo Anti-inflammatory Activity of Pyrazoline Clubbed Thiazolinone Derivatives
    作者:Deepak Kumar Singh、Mayank Kulshreshtha、Yogesh Kumar、Pooja A. Chawla、Akash Ved、Karuna Shanker Shukla
    DOI:10.2174/1570178617999201106113114
    日期:2021.7.29
    <p>The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities, including inflammatory action. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure. Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant, etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have a significant anti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate it as an anti-inflammatory agent.</p> </sec> <sec> <title /> <p>In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a threestep reaction. The compounds were subjected to spectral analysis by Infrared, Mass, and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized derivatives were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina.</p> </sec> <sec> <title /> <p>Compounds PT-1, PT-3, PT-4, and PT-8 exhibited significant anti-inflammatory activity at 3rd hour, being 50.7%, 54.3%, 52.3%, and 57%, respectively, closer to that of the standard drug indomethacin (61.9%). From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed a docking score of -6.5 kJ/mol, compound PT-1 exhibited the highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 had a docking score of 9.4 kJ/mol for COX-2.</p> </sec> <sec> <title /> <p>It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors was very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.</p> </sec></div> <div class="value-text ch">吡唑啉类化合物在其对高锰酸盐和新生氢的反应中表现出与不饱和化合物相似的行为,类似于脂肪衍生物。这种核与各种生物活性有关,包括炎症作用。噻唑酮是一种含有硫和氮原子以及羰基的杂环化合物。由于其多种生物活性,如抗炎、抗微生物、抗增殖、抗病毒、抗抽搐等,噻唑酮及其衍生物一直受到持续关注。研究的目的是将吡唑啉核与噻唑酮结合,以获得显著的抗炎活性。合成的化合物在化学上被表征以确定其化学结构,并评估其作为抗炎药物的效果。 在本研究中,通过三步反应合成了八种取代吡唑啉衍生物(PT1-PT8)。这些化合物经过红外、质谱和核磁共振光谱以及元素分析数据的光谱分析。所有合成的衍生物均评估了它们的体内抗炎活性。通过使用吲哚美辛作为参考化合物,评估了合成衍生物对COX-1和COX-2的亲和力,通过AutoDock Vina进行分子对接可视化。 化合物PT-1、PT-3、PT-4和PT-8在第3小时表现出显著的抗炎活性,分别为50.7%、54.3%、52.3%和57%,接近标准药物吲哚美辛(61.9%)的效果。从选定的抗炎靶点来看,合成的衍生物与COX-1和COX-2受体的相互作用更好,吲哚美辛的对接分数为-6.5 kJ/mol,化合物PT-1在COX-1上表现出最高的对接分数为-9.1 kJ/mol,而化合物PT-8在COX-2上的对接分数为9.4 kJ/mol。 结论是合成的衍生物与COX-2受体的相互作用比与COX-1受体的相互作用更多,因为与COX-2受体的对接分数非常好。可以得出结论,合成的衍生物(PT-1至PT-8)是有效的COX-2抑制剂。</div> </div> </li> </ul> <a href="https://chem.molaid.com/material/detail?source=UserSourcePortal&id=3101932r5b45adfb51N0&inchikey=QTKUEXSSQYRHHA-WEVVVXLNSA-N" target="_blank" rel="nofollow" class="view-more">查看更多</a> </div> <div class="module" id="tongleihuahewu"> <h3 class="module-title"><i class="iconfont icon-tongleihuahewu"></i>同类化合物</h3> <div class="compounds-list"> <a target="_blank" href="https://www.molaid.com/MS_145" class="compound-item" title="(2Z)-1,3-二苯基-2-丙烯-1-酮,2-丙烯-1-酮,1,3-二苯基-,(2Z)-">(2Z)-1,3-二苯基-2-丙烯-1-酮,2-丙烯-1-酮,1,3-二苯基-,(2Z)-</a> <a target="_blank" href="https://www.molaid.com/MS_218" class="compound-item" title="龙血素D">龙血素D</a> <a target="_blank" href="https://www.molaid.com/MS_220" class="compound-item" title="龙血素A">龙血素A</a> <a target="_blank" href="https://www.molaid.com/MS_221" class="compound-item" title="龙血素 B">龙血素 B</a> <a target="_blank" href="https://www.molaid.com/MS_407" class="compound-item" title="黄色当归醇F">黄色当归醇F</a> <a target="_blank" href="https://www.molaid.com/MS_408" class="compound-item" title="黄色当归醇B">黄色当归醇B</a> <a target="_blank" href="https://www.molaid.com/MS_409" class="compound-item" title="黄腐醇; 黄腐酚">黄腐醇; 黄腐酚</a> 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title="苯乙酰腈,a-(1-氨基-2-苯基亚乙基)-">苯乙酰腈,a-(1-氨基-2-苯基亚乙基)-</a> <a target="_blank" href="https://www.molaid.com/MS_14253" class="compound-item" title="苏木查耳酮">苏木查耳酮</a> <a target="_blank" href="https://www.molaid.com/MS_14453" class="compound-item" title="苄桂哌酯">苄桂哌酯</a> <a target="_blank" href="https://www.molaid.com/MS_15288" class="compound-item" title="芦荟提取物">芦荟提取物</a> <a target="_blank" href="https://www.molaid.com/MS_15859" class="compound-item" title="腈苯唑">腈苯唑</a> <a target="_blank" href="https://www.molaid.com/MS_16513" class="compound-item" title="胀果甘草宁C">胀果甘草宁C</a> <a target="_blank" href="https://www.molaid.com/MS_16909" class="compound-item" title="聚磷酸根皮酚">聚磷酸根皮酚</a> <a target="_blank" href="https://www.molaid.com/MS_16918" class="compound-item" title="聚硫橡胶">聚硫橡胶</a> <a target="_blank" href="https://www.molaid.com/MS_17398" class="compound-item" title="羥亞苄乙醯苯">羥亞苄乙醯苯</a> <a target="_blank" href="https://www.molaid.com/MS_17961" class="compound-item" title="美托查酮">美托查酮</a> <a target="_blank" href="https://www.molaid.com/MS_18731" class="compound-item" title="紫铆因">紫铆因</a> <a target="_blank" href="https://www.molaid.com/MS_19095" class="compound-item" title="米拉贝格隆杂质23">米拉贝格隆杂质23</a> <a target="_blank" href="https://www.molaid.com/MS_19130" class="compound-item" title="米卡芬净钠中间体">米卡芬净钠中间体</a> <a target="_blank" href="https://www.molaid.com/MS_21400" class="compound-item" title="硫酸二甲酯">硫酸二甲酯</a> <a target="_blank" href="https://www.molaid.com/MS_22651" class="compound-item" title="硅烷,[(1,3-二苯基-1-丙烯基)氧代]三甲基-">硅烷,[(1,3-二苯基-1-丙烯基)氧代]三甲基-</a> <a target="_blank" href="https://www.molaid.com/MS_23316" class="compound-item" title="盐酸普罗帕酮">盐酸普罗帕酮</a> <a target="_blank" href="https://www.molaid.com/MS_23590" class="compound-item" title="盐酸依他苯酮">盐酸依他苯酮</a> <a target="_blank" href="https://www.molaid.com/MS_23703" class="compound-item" title="盐(1:1)[1,1'-联苯基]-2,2'-二磺酸,4,4'-二[2-[1-[[(2,4-二甲基苯基)氨基]羰基]-2-羰基丙基]二氮烯基]-,钙">盐(1:1)[1,1'-联苯基]-2,2'-二磺酸,4,4'-二[2-[1-[[(2,4-二甲基苯基)氨基]羰基]-2-羰基丙基]二氮烯基]-,钙</a> </div> </div> <div class="module" id="xiangguanjiegoufenlei"> <h3 class="module-title"><i class="iconfont icon-xiangguanjiegoufenlei"></i>相关结构分类</h3> <div class="compounds-list"> <a href="https://www.molaid.com/fenzi/10" class="compound-item" title="有机杂环化合物">有机杂环化合物</a> <a href="https://www.molaid.com/fenzi/11" class="compound-item" title="苯类化合物">苯类化合物</a> <a href="https://www.molaid.com/fenzi/12" class="compound-item" title="木脂素、新木脂素和相关化合物">木脂素、新木脂素和相关化合物</a> <a href="https://www.molaid.com/fenzi/13" class="compound-item" title="苯丙烷和聚酮">苯丙烷和聚酮</a> <a href="https://www.molaid.com/fenzi/14" class="compound-item" title="脂质和类脂质分子">脂质和类脂质分子</a> <a href="https://www.molaid.com/fenzi/15" class="compound-item" title="有机酸及其衍生物">有机酸及其衍生物</a> <a href="https://www.molaid.com/fenzi/16" class="compound-item" title="有机氧化合物">有机氧化合物</a> <a href="https://www.molaid.com/fenzi/17" class="compound-item" title="生物碱及其衍生物">生物碱及其衍生物</a> <a href="https://www.molaid.com/fenzi/18" class="compound-item" title="有机硫化合物">有机硫化合物</a> <a href="https://www.molaid.com/fenzi/19" class="compound-item" title="核苷、核苷酸和类似物">核苷、核苷酸和类似物</a> <a href="https://www.molaid.com/fenzi/20" class="compound-item" title="碳氢化合物衍生物">碳氢化合物衍生物</a> <a href="https://www.molaid.com/fenzi/21" class="compound-item" title="有机氮化合物">有机氮化合物</a> <a href="https://www.molaid.com/fenzi/22" class="compound-item" title="碳氢化合物">碳氢化合物</a> <a href="https://www.molaid.com/fenzi/23" class="compound-item" title="有机卤素化合物">有机卤素化合物</a> <a href="https://www.molaid.com/fenzi/24" class="compound-item" title="有机聚合物">有机聚合物</a> <a href="https://www.molaid.com/fenzi/25" class="compound-item" title="有机金属化合物">有机金属化合物</a> <a href="https://www.molaid.com/fenzi/26" class="compound-item" title="乙炔化物 ">乙炔化物 </a> <a href="https://www.molaid.com/fenzi/27" class="compound-item" title="有机磷化合物">有机磷化合物</a> <a href="https://www.molaid.com/fenzi/28" class="compound-item" title="叠烯">叠烯</a> <a href="https://www.molaid.com/fenzi/29" class="compound-item" title="有机1,3-偶极化合物">有机1,3-偶极化合物</a> <a href="https://www.molaid.com/fenzi/30" class="compound-item" title="碳化物">碳化物</a> <a href="https://www.molaid.com/fenzi/31" class="compound-item" title="有机盐">有机盐</a> <a href="https://www.molaid.com/fenzi/32" class="compound-item" title="有机阳离子">有机阳离子</a> <a href="https://www.molaid.com/fenzi/33" class="compound-item" title="卡宾">卡宾</a> <a href="https://www.molaid.com/fenzi/34" class="compound-item" title="有机阴离子">有机阴离子</a> </div> </div> </div> <div class="right"> <div class="module"> <link rel="stylesheet" href="https://www.molaid.com/assets/css/common/hot-molecular.css?v=202504271"> <div class="component-card hot-molecular-card" style="--color: #FF4539;"> <div class="title"> <h3 class="title-name">热门分子</h3> </div> <div class="card-content"> <ul class="list"> <li class="item item-special" data-sort="TOP"> 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src="data:image/svg+xml;base64,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