N-methoxy>methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 糖脂
• 英文名称: N-methoxy>methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide
• 英文别名: methyl 6-[[2-[[1,3-bis[2-[2-[2-[2-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyethoxy]ethoxy]ethoxy]ethoxymethoxy]-2-[2-[2-[2-[2-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyethoxy]ethoxy]ethoxy]ethoxymethoxymethyl]propan-2-yl]amino]-2-oxoethyl]amino]-6-oxohexanoate
• 化学式: C₅₈H₁₀₈N₂O₃₇
• 分子量: 1425.49
• InChiKey: IXEKBBHTNZATPL-RTLYOTQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -9.5
• 重原子数：
  97
• 可旋转键数：
  63
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  521
• 氢给体数：
  14
• 氢受体数：
  37

反应信息

• 作为反应物：
  描述：

  N-methoxy>methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.25h， 生成 N-<methyl>-N^α-(1-adipyl)glycinamide
  参考文献：
  名称：

  对三萜半乳糖苷的胆固醇衍生物具有很高的对肝脏脱唾液酸糖蛋白受体的亲和力：一种有效的降胆固醇剂。

  摘要：

  已经设计出胆固醇衍生的半乳糖苷，以通过在肝脏中识别半乳糖的去唾液酸糖蛋白受体诱导肝脏摄取脂蛋白。在这项研究中，我们描述了对脱唾液酸糖蛋白受体N-[[tris-O-（3,6,9-trioxaundecanyl-beta-D-galactopyranosyl）metho xym乙基]高亲和力的新开发的三天线簇半乳糖苷的衍生化Nα-[1-（6-甲基己二酰基）]甘氨酰胺（TG（20A））与胆固醇。到此为止，在（苯并三唑-1-基氧基）三（二甲基氨基）六氟磷酸phosph存在下，TG（20A）与甘氨酸-（5-胆甾烯-3β-酯）偶联，得到N-[[tris-O-（ 3,6,9-三氧杂十二烷基-β-D-吡喃并吡喃半乳糖基）甲氧基甲基]甲基] -Nα-[1-（1-（6-（5-胆甾烯-3β-酰氧基）甘氨酰基）己二酰基]甘氨酰胺（TG（20A）C）收率为46％。这种化合物是两亲的，水溶性化合物。在水溶液中，它容易形成由约20个分子组成的小胶束（4

  DOI：

  10.1021/jm00011a003
• 作为产物：
  描述：

  N-methoxy>methyl>methyl>-N^α-<1-(6-methyladipyl)>glycinamide 在 potassium tert-butylate 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 4.0h， 以77%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

文献信息

• The Cholesterol Derivative of a Triantennary Galactoside with High Affinity for the Hepatic Asialoglycoprotein Receptor: a Potent Cholesterol Lowering Agent
  作者：E. A. L. Biessen、H. Broxterman、J. H. Van Boom、Th. J. C. Van Berkel

  DOI：10.1021/jm00011a003

  日期：1995.5

  dose-dependent decrease in the serum cholesterol content of maximally 44%, at a dose of 1.9 mg kg-1. This makes TG(20A)C at least 30-fold more effective than the previously developed N-[[tris-O-(beta-D-galactopyranosyl)methyl]methyl]-N alpha-[4-(5- cholesten-3 beta-yloxy)succinyl]glycinamide (TG(4A)C), provided with a cluster galactoside that displayed a 2000-fold lower affinity for the asialoglycoprotein

  已经设计出胆固醇衍生的半乳糖苷，以通过在肝脏中识别半乳糖的去唾液酸糖蛋白受体诱导肝脏摄取脂蛋白。在这项研究中，我们描述了对脱唾液酸糖蛋白受体N-[[tris-O-（3,6,9-trioxaundecanyl-beta-D-galactopyranosyl）metho xym乙基]高亲和力的新开发的三天线簇半乳糖苷的衍生化Nα-[1-（6-甲基己二酰基）]甘氨酰胺（TG（20A））与胆固醇。到此为止，在（苯并三唑-1-基氧基）三（二甲基氨基）六氟磷酸phosph存在下，TG（20A）与甘氨酸-（5-胆甾烯-3β-酯）偶联，得到N-[[tris-O-（ 3,6,9-三氧杂十二烷基-β-D-吡喃并吡喃半乳糖基）甲氧基甲基]甲基] -Nα-[1-（1-（6-（5-胆甾烯-3β-酰氧基）甘氨酰基）己二酰基]甘氨酰胺（TG（20A）C）收率为46％。这种化合物是两亲的，水溶性化合物。在水溶液中，它容易形成由约20个分子组成的小胶束（4
• 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.