N-methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide | 159339-57-8

• 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: N-methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide
• 英文别名: Methyl 6-[[2-[[1,3-bis(methylsulfanylmethoxy)-2-(methylsulfanylmethoxymethyl)propan-2-yl]amino]-2-oxoethyl]amino]-6-oxohexanoate
• CAS: 159339-57-8
• 化学式: C₁₉H₃₆N₂O₇S₃
• 分子量: 500.702
• InChiKey: PHCMNQJEKKEXRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  31
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  188
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide 、 3-hydroxypropyl 2',3',4',6'-tetra-O-benzoyl-β-D-galactopyranoside 在 N-碘代丁二酰亚胺 、 三氟甲磺酸 、 4 A molecular sieve 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以28%的产率得到N-methoxy>methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide
  参考文献：
  名称：

  Synthesis of Cluster Galactosides with High Affinity for the Hepatic Asialoglycoprotein Receptor

  摘要：

  High-affinity Ligands for the asialoglycoprotein receptor, which is uniquely localized on the parenchymal liver cell and recognizes oligoantennary galactosides, might be utilized as homing device to specifically target drugs or genes to parenchymal liver cells. In the present study, the synthesis of galactose-terminated triantennary glycosides, provided with various spacers between the beta-galactopyranosyl moieties and the branching point of the dendrite, is described. N-[Tris[[(methylthio)methoxy]methyl]methyl]-N-alpha-[1-(6-methyladipy)]glycinamide (3b) was glycosylated with monogalactosyl derivatives, containing propanediol or ethylene glycol units as hydrophilic spacer moieties, to yield the corresponding cluster galactosides. To determine the affinity of the cluster galactosides for the asialoglycoprotein receptor, we have performed competition studies of [I-125]ASOR binding, a specific ligand for the asialoglycoprotein receptor, to isolated parenchymal cells. The affinity for the asialoglycoprotein receptor significantly increased with increasing spacer length. N-[[[Tris-O-(beta-D-galactopyranosyl)-3,6,9-trioxaundecanoxy]methoxy]methyl]-N-alpha-[1-(6-methyladipyl)]glycinamide (4e), a cluster galactoside provided with a 20 Angstrom spacer, possessed an at least 2000-fold higher affinity for the receptor than N-[[tris-O-(beta-D-galactopyranosyl)methyl]methyl]-N-alpha -[1-(6-methyladipyl)]glycinamide (4a), a cluster galactoside lacking the spacer. It is concluded that vicinal galactosyl moieties within a cluster galactoside are more optimal recognized by the galactose binding sites of the asialoglycoprotein receptor upon proper spacing. The most potent galactoside, TG(20 Angstrom), may constitute an attractive targeting device for the specific delivery of drugs and/or genes to the parenchymal liver cell.

  DOI：

  10.1021/jm00009a014
• 作为产物：
  描述：

  脂肪酸甲酯 在 N,N'-二环己基碳二亚胺 、 过氧化苯甲酰 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 8.0h， 生成 N-methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide
  参考文献：
  名称：

  Synthesis of Cluster Galactosides with High Affinity for the Hepatic Asialoglycoprotein Receptor

  摘要：

  High-affinity Ligands for the asialoglycoprotein receptor, which is uniquely localized on the parenchymal liver cell and recognizes oligoantennary galactosides, might be utilized as homing device to specifically target drugs or genes to parenchymal liver cells. In the present study, the synthesis of galactose-terminated triantennary glycosides, provided with various spacers between the beta-galactopyranosyl moieties and the branching point of the dendrite, is described. N-[Tris[[(methylthio)methoxy]methyl]methyl]-N-alpha-[1-(6-methyladipy)]glycinamide (3b) was glycosylated with monogalactosyl derivatives, containing propanediol or ethylene glycol units as hydrophilic spacer moieties, to yield the corresponding cluster galactosides. To determine the affinity of the cluster galactosides for the asialoglycoprotein receptor, we have performed competition studies of [I-125]ASOR binding, a specific ligand for the asialoglycoprotein receptor, to isolated parenchymal cells. The affinity for the asialoglycoprotein receptor significantly increased with increasing spacer length. N-[[[Tris-O-(beta-D-galactopyranosyl)-3,6,9-trioxaundecanoxy]methoxy]methyl]-N-alpha-[1-(6-methyladipyl)]glycinamide (4e), a cluster galactoside provided with a 20 Angstrom spacer, possessed an at least 2000-fold higher affinity for the receptor than N-[[tris-O-(beta-D-galactopyranosyl)methyl]methyl]-N-alpha -[1-(6-methyladipyl)]glycinamide (4a), a cluster galactoside lacking the spacer. It is concluded that vicinal galactosyl moieties within a cluster galactoside are more optimal recognized by the galactose binding sites of the asialoglycoprotein receptor upon proper spacing. The most potent galactoside, TG(20 Angstrom), may constitute an attractive targeting device for the specific delivery of drugs and/or genes to the parenchymal liver cell.

  DOI：

  10.1021/jm00009a014

文献信息

• Synthesis of Cluster Galactosides with High Affinity for the Hepatic Asialoglycoprotein Receptor
  作者：Erik A. L. Biessen、Diana M. Beuting、Harlof C. P. F. Roelen、Gijs A. van de Marel、Jacques H. Van Boom、Theo J. C. Van Berkel

  DOI：10.1021/jm00009a014

  日期：1995.4

  High-affinity Ligands for the asialoglycoprotein receptor, which is uniquely localized on the parenchymal liver cell and recognizes oligoantennary galactosides, might be utilized as homing device to specifically target drugs or genes to parenchymal liver cells. In the present study, the synthesis of galactose-terminated triantennary glycosides, provided with various spacers between the beta-galactopyranosyl moieties and the branching point of the dendrite, is described. N-[Tris[[(methylthio)methoxy]methyl]methyl]-N-alpha-[1-(6-methyladipy)]glycinamide (3b) was glycosylated with monogalactosyl derivatives, containing propanediol or ethylene glycol units as hydrophilic spacer moieties, to yield the corresponding cluster galactosides. To determine the affinity of the cluster galactosides for the asialoglycoprotein receptor, we have performed competition studies of [I-125]ASOR binding, a specific ligand for the asialoglycoprotein receptor, to isolated parenchymal cells. The affinity for the asialoglycoprotein receptor significantly increased with increasing spacer length. N-[[[Tris-O-(beta-D-galactopyranosyl)-3,6,9-trioxaundecanoxy]methoxy]methyl]-N-alpha-[1-(6-methyladipyl)]glycinamide (4e), a cluster galactoside provided with a 20 Angstrom spacer, possessed an at least 2000-fold higher affinity for the receptor than N-[[tris-O-(beta-D-galactopyranosyl)methyl]methyl]-N-alpha -[1-(6-methyladipyl)]glycinamide (4a), a cluster galactoside lacking the spacer. It is concluded that vicinal galactosyl moieties within a cluster galactoside are more optimal recognized by the galactose binding sites of the asialoglycoprotein receptor upon proper spacing. The most potent galactoside, TG(20 Angstrom), may constitute an attractive targeting device for the specific delivery of drugs and/or genes to the parenchymal liver cell.