N-(1-methylethyl)-3-(4-methoxy-3-methylphenyl)-(E)-propenamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: N-(1-methylethyl)-3-(4-methoxy-3-methylphenyl)-(E)-propenamide
• 英文别名: (E)-3-(4-methoxy-3-methylphenyl)-N-propan-2-ylprop-2-enamide
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: UTYMKZPOEWODLS-SOFGYWHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-甲基苯甲醚 在 六甲基磷酰三胺 、 碘 、 palladium diacetate 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 silver nitrate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.5h， 生成 N-(1-methylethyl)-3-(4-methoxy-3-methylphenyl)-(E)-propenamide
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Difluoromethyl Cinnamoyl Amides

  摘要：

  通过取代酚羟基为二氟甲基基团，合成了一系列异麦芽酸新酰胺，并对其进行了体外抗菌活性测试，针对十四种细菌菌株（六种革兰氏阳性和八种革兰氏阴性）。开发了一种一锅法，利用Deoxofluor®作为氟化试剂，获得了3′-(二氟甲基)-4′-甲氧基肉桂酰胺。N-异丙基、N-异戊基和N-(2-苯乙基)酰胺11b、11d和11g对斯米格马分枝杆菌（MIC = 8 µg/mL）具有最高活性和选择性，其中11b和11g对HepG2和A549细胞几乎没有细胞毒性或无细胞毒性。还合成了N-异丙基酰胺11b的十三个类似物，并对其抗菌活性进行了测试。结果显示，二氟甲基基团增强了抗菌活性，并增加了对斯米格马分枝杆菌的选择性，改变了母体化合物的微生物抑制谱。一些化合物对斯米格马分枝杆菌表现出的选择性使它们成为在寻找针对结核分枝杆菌的新窄谱抗生素的潜在引物。

  DOI：

  10.3390/molecules25040789

文献信息

• [EN] COMPOUNDS HAVING ANTIBACTERIAL ACTIVITY, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM<br/>[FR] COMPOSÉS AYANT UNE ACTIVITÉ ANTIBACTÉRIENNE, PROCÉDÉ POUR LEUR PRÉPARATION ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT
  申请人：CONSEJO NAC INVEST CIENT TEC

  公开号：WO2013105053A1

  公开（公告）日：2013-07-18

  A compound of the structural formula I, a pharmaceutically acceptable salt, prodrug or derivative thereof, characterized in that R1 is selected from H, a linear or branched (C1-C5) alkyl group and a COR4 group; R2 is selected from H, a linear or branched (C1-C5) alkyl group and a COR5 group; R3 is selected from H, a linear or branched (C1-C5) alkyl group, a linear or branched (C1-C5)- O-alkyl group, a cycloalkyl of (C5-C6) carbon atoms, an aryl group, and an aryl (C1-C5) alkyl group wherein the aryl group can be an unsubstituted aryl or an aryl substituted with one or more R6 groups and an NHCOR5 group, or the R2 and R3 groups together with N may form a substituted or unsubstituted piperidine, morpholine or piperazine group; R4 is selected from H and a (C1-C5) alkyl group; R5 is selected from an unsubstituted aryl group or an aryl group substituted with one or more R6, linear or branched (C1-C5) alkyl or pyridyne groups and a pyridine group; R6 is selected from (C1-C5) alkyl groups, halogen and nitro, provided that R1, R2 and R3 are not H atoms at the same time. The compounds present antibacterial activity. Process for their preparation and pharmaceutical compositions comprising them are also disclosed.

  化合物的结构式I，其药学上可接受的盐、前药或衍生物，其特征在于：R1选自H、线性或支链（C1-C5）烷基和COR4基团；R2选自H、线性或支链（C1-C5）烷基和COR5基团；R3选自H、线性或支链（C1-C5）烷基、线性或支链（C1-C5）-O-烷基、（C5-C6）碳原子的环烷基、芳基和芳基（C1-C5）烷基，其中芳基可以是未取代的芳基或带有一个或多个R6基团和NHCOR5基团的取代芳基，或者R2和R3基团与N一起可以形成取代或未取代的哌啶、吗啉或哌嗪基团；R4选自H和（C1-C5）烷基；R5选自未取代的芳基或带有一个或多个R6、线性或支链（C1-C5）烷基或吡啶基团和吡啶基团的取代芳基；R6选自（C1-C5）烷基、卤素和硝基，前提是R1、R2和R3不能同时为H原子。这些化合物具有抗菌活性。还公开了它们的制备方法和包含它们的制药组合物。
• COMPOUNDS HAVING ANTIBACTERIAL ACTIVITY, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
  申请人：Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET)

  公开号：US20140357678A1

  公开（公告）日：2014-12-04

  A pharmaceutically acceptable salt, prodrug or derivative compound of the formula I, wherein R 1 is selected from H, a (C1-C5) alkyl group and a COR 4 group; R 2 is selected from H, a (C1-C5) alkyl group and a COR 5 group; R 3 is selected from H, a (C1-C5) alkyl group, a (C1-C5)-O-alkyl group, a cycloalkyl of (C5-C6) carbon atoms, an aryl group, and an aryl (C1-C5) alkyl group wherein the aryl group can be an unsubstituted aryl or substituted with one or more R 6 groups and an NHCOR 5 group, or the R 2 and R 3 groups together with N may form a piperidine, morpholine or piperazine group; R 4 is selected from H and a (C1-C5)alkyl group; R 5 is selected from an aryl group unsubstituted or substituted with one or more R 6 , linear or branched(C1-C5) alkyl or pyridyne groups and a pyridine group; R 6 is selected from (C1-C5)alkyl groups, halogen and nitro.

  公认药用盐、前药或衍生物化合物的公式I，其中R1选择自H、(C1-C5)烷基和COR4基团；R2选择自H、(C1-C5)烷基和COR5基团；R3选择自H、(C1-C5)烷基、(C1-C5)-O-烷基、含有(C5-C6)碳原子的环烷基、芳基和芳基(C1-C5)烷基，其中芳基可以是未取代的芳基或取代有一个或多个R6基团和NHCOR5基团的芳基，或者R2和R3基团与N一起形成哌啶、吗啉或哌嗪基团；R4选择自H和(C1-C5)烷基；R5选择自未取代或取代有一个或多个R6、线性或支链(C1-C5)烷基或吡啶基团和吡啶基团的芳基基团；R6选择自(C1-C5)烷基、卤素和硝基。
• US9255071B2
  申请人：——

  公开号：US9255071B2

  公开（公告）日：2016-02-09
• Synthesis and Antibacterial Activity of Difluoromethyl Cinnamoyl Amides
  作者：Mario David Martínez、Diego Ariel Riva、Cybele Garcia、Fernando Javier Durán、Gerardo Burton

  DOI：10.3390/molecules25040789

  日期：——

  Series of novel amides of isoferulic acid, where the phenolic hydroxyl was replaced by a difluoromethyl group, were synthesized and their in vitro antibacterial activities assayed against fourteen bacterial strains (six Gram-positive and eight Gram-negative). A one-pot methodology was developed to obtain the 3′-(difluoromethyl)-4′-methoxycinnamoyl amides using Deoxofluor® as a fluorinating agent. The N-isopropyl, N-isopentyl, and N-(2-phenylethyl) amides 11b, 11d and 11g were the most active and selective against Mycobacterium smegmatis (MIC = 8 µg/mL) with 11b and 11g displaying negligible or no cytotoxicity against HepG2 and A549 cells. Thirteen analogs of N-isopropylamide 11b were also synthesized and their antibacterial activity assayed. Results show that the difluoromethyl moiety enhanced antibacterial activity and selectivity towards M. smegmatis, changing the microorganism inhibition profile of the parent compound. The selectivity exhibited by some of the compounds towards M. smegmatis makes them potential leads in the search for new narrow spectrum antibiotics against M. tuberculosis.

  通过取代酚羟基为二氟甲基基团，合成了一系列异麦芽酸新酰胺，并对其进行了体外抗菌活性测试，针对十四种细菌菌株（六种革兰氏阳性和八种革兰氏阴性）。开发了一种一锅法，利用Deoxofluor®作为氟化试剂，获得了3′-(二氟甲基)-4′-甲氧基肉桂酰胺。N-异丙基、N-异戊基和N-(2-苯乙基)酰胺11b、11d和11g对斯米格马分枝杆菌（MIC = 8 µg/mL）具有最高活性和选择性，其中11b和11g对HepG2和A549细胞几乎没有细胞毒性或无细胞毒性。还合成了N-异丙基酰胺11b的十三个类似物，并对其抗菌活性进行了测试。结果显示，二氟甲基基团增强了抗菌活性，并增加了对斯米格马分枝杆菌的选择性，改变了母体化合物的微生物抑制谱。一些化合物对斯米格马分枝杆菌表现出的选择性使它们成为在寻找针对结核分枝杆菌的新窄谱抗生素的潜在引物。