(2S)-2-(1,3-dioxoisoindol-2-yl)-3-[2-[[[(2S)-1-methoxy-1-oxohexan-2-yl]amino]methyl]phenyl]propanoic acid | 1413323-89-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-2-(1,3-dioxoisoindol-2-yl)-3-[2-[[[(2S)-1-methoxy-1-oxohexan-2-yl]amino]methyl]phenyl]propanoic acid
• CAS: 1413323-89-3
• 化学式: C₂₅H₂₈N₂O₆
• 分子量: 452.507
• InChiKey: NVODFAUFMGTPFO-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-2-(1,3-dioxoisoindol-2-yl)-3-[2-[[[(2S)-1-methoxy-1-oxohexan-2-yl]amino]methyl]phenyl]propanoic acid 在 吡啶 、 盐酸 、 N,N'-二环己基碳二亚胺 作用下， 以 水 、 丙酮 、 乙腈 为溶剂， 反应 30.0h， 生成 4(S)-butyl-4(S)-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1,3,4,5-tetrahydro-3-oxo-2H-2-benzazepine-2-acetic acid
  参考文献：
  名称：

  Variation of the Net Charge, Lipophilicity, and Side Chain Flexibility in Dmt¹-DALDA: Effect on Opioid Activity and Biodistribution

  摘要：

  The influence of the side chain charges of the second and fourth amino acid residues in the peptidic mu opioid lead agonist Dmt-D-Arg-Phe-Lys-NH2. ([Dmt(1)-DALDA) was examined. Additionally, to increase the overall lipophilicity of [Dmt(1)]-DALDA and to investigate the Phe(3) side chain flexibility, the final amide bond was N-methylated and Phe(3) was replaced by a constrained aminobenzazepine analogue. The in vitro receptor binding and activity of the peptides, as well as their in vivo transport (brain in- and efflux and tissue biodistribution) and antinociceptive properties after peripheral administration (ip and sc) in mice were determined. The structural modifications result in significant shifts of receptor binding, activity, and transport, properties. Strikingly, while [Dmt(1)]-DALDA and its N-methyl analogue, Dmt-D-Arg-Phe-NMeLys-NH2, showed a long-lasting antinociceptive effect (>7 h), the peptides with D-Cit(2) generate potent antinociception more rapidly (maximal effect at 1h postinjection) but also lose their analgesic activity faster when compared to [Dmt(1)]-DALDA. and [Dmit(1),NMeLys(4)]-DALDA.

  DOI：

  10.1021/jm3008079
• 作为产物：
  描述：

  (S)-N,N-phthaloyl-o-cyanophenylalanine 在 吡啶 、 水 、 氢气 、 sodium cyanoborohydride 、 magnesium sulfate 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 20.0~50.0 ℃ 、344.75 kPa 条件下， 反应 52.0h， 生成 (2S)-2-(1,3-dioxoisoindol-2-yl)-3-[2-[[[(2S)-1-methoxy-1-oxohexan-2-yl]amino]methyl]phenyl]propanoic acid
  参考文献：
  名称：

  Variation of the Net Charge, Lipophilicity, and Side Chain Flexibility in Dmt¹-DALDA: Effect on Opioid Activity and Biodistribution

  摘要：

  The influence of the side chain charges of the second and fourth amino acid residues in the peptidic mu opioid lead agonist Dmt-D-Arg-Phe-Lys-NH2. ([Dmt(1)-DALDA) was examined. Additionally, to increase the overall lipophilicity of [Dmt(1)]-DALDA and to investigate the Phe(3) side chain flexibility, the final amide bond was N-methylated and Phe(3) was replaced by a constrained aminobenzazepine analogue. The in vitro receptor binding and activity of the peptides, as well as their in vivo transport (brain in- and efflux and tissue biodistribution) and antinociceptive properties after peripheral administration (ip and sc) in mice were determined. The structural modifications result in significant shifts of receptor binding, activity, and transport, properties. Strikingly, while [Dmt(1)]-DALDA and its N-methyl analogue, Dmt-D-Arg-Phe-NMeLys-NH2, showed a long-lasting antinociceptive effect (>7 h), the peptides with D-Cit(2) generate potent antinociception more rapidly (maximal effect at 1h postinjection) but also lose their analgesic activity faster when compared to [Dmt(1)]-DALDA. and [Dmit(1),NMeLys(4)]-DALDA.

  DOI：

  10.1021/jm3008079

文献信息

• Variation of the Net Charge, Lipophilicity, and Side Chain Flexibility in Dmt¹-DALDA: Effect on Opioid Activity and Biodistribution
  作者：Alexandre Novoa、Sylvia Van Dorpe、Evelien Wynendaele、Mariana Spetea、Nathalie Bracke、Sofie Stalmans、Cecilia Betti、Nga N. Chung、Carole Lemieux、Johannes Zuegg、Matthew A. Cooper、Dirk Tourwé、Bart De Spiegeleer、Peter W. Schiller、Steven Ballet

  DOI：10.1021/jm3008079

  日期：2012.11.26

  The influence of the side chain charges of the second and fourth amino acid residues in the peptidic mu opioid lead agonist Dmt-D-Arg-Phe-Lys-NH2. ([Dmt(1)-DALDA) was examined. Additionally, to increase the overall lipophilicity of [Dmt(1)]-DALDA and to investigate the Phe(3) side chain flexibility, the final amide bond was N-methylated and Phe(3) was replaced by a constrained aminobenzazepine analogue. The in vitro receptor binding and activity of the peptides, as well as their in vivo transport (brain in- and efflux and tissue biodistribution) and antinociceptive properties after peripheral administration (ip and sc) in mice were determined. The structural modifications result in significant shifts of receptor binding, activity, and transport, properties. Strikingly, while [Dmt(1)]-DALDA and its N-methyl analogue, Dmt-D-Arg-Phe-NMeLys-NH2, showed a long-lasting antinociceptive effect (>7 h), the peptides with D-Cit(2) generate potent antinociception more rapidly (maximal effect at 1h postinjection) but also lose their analgesic activity faster when compared to [Dmt(1)]-DALDA. and [Dmit(1),NMeLys(4)]-DALDA.