trans-3-(3,4-dimethoxybenzylcarbamoyl)propenoic acid | 1164484-33-6

• 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: trans-3-(3,4-dimethoxybenzylcarbamoyl)propenoic acid
• 英文别名: HOOCCH=CHCONHCH2Ph-3,4-OCH3；3-(N-((3,4-Dimethoxyphenyl)methyl)carbamoyl)prop-2-enoic acid；(E)-4-[(3,4-dimethoxyphenyl)methylamino]-4-oxobut-2-enoic acid
• CAS: 1164484-33-6
• 化学式: C₁₃H₁₅NO₅
• mdl: MFCD01574972
• 分子量: 265.266
• InChiKey: FPYJEXFGDFMOOG-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-3-(3,4-dimethoxybenzylcarbamoyl)propenoic acid 、 Mu-Ala-NH-NH-CH2CONH2 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以14%的产率得到N2-(N-piperidinylcarbonylalanyl)-N1-(carbamoylmethyl)-N1-trans-(3-(3,4-dimethoxybenzyl)carbamoylpropenoyl)hydrazine
  参考文献：
  名称：

  Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)

  摘要：

  Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CH=CHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively, are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P1' position, and potency increased as we increased the hydrophobicity of the inhibitor in this position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs.

  DOI：

  10.1021/jm900849h
• 作为产物：
  描述：

  trans-3-(3,4-dimethoxybenzylcarbamoyl)propenoic acid ethyl ester 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以72%的产率得到trans-3-(3,4-dimethoxybenzylcarbamoyl)propenoic acid
  参考文献：
  名称：

  Aza-Peptidyl Michael Acceptor and Epoxide Inhibitors—Potent and Selective Inhibitors of Schistosoma mansoni and Ixodes ricinus Legumains (Asparaginyl Endopeptidases)

  摘要：

  Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CH=CHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively, are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P1' position, and potency increased as we increased the hydrophobicity of the inhibitor in this position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs.

  DOI：

  10.1021/jm900849h