glycyl-Tris | 159339-55-6

• 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: glycyl-Tris
• 英文别名: N-[tris(hydroxymethyl)methyl]glycinamide；N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycinamide；Gly-Tris；Acetamide, 2-amino-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]-；2-amino-N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]acetamide
• CAS: 159339-55-6
• 化学式: C₆H₁₄N₂O₄
• 分子量: 178.188
• InChiKey: YGWHCOGDUMDXKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  116
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  glycyl-Tris 在 过氧化苯甲酰 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.0h， 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
• 作为产物：
  描述：

  N-<2-hydroxy-1,1-bis(hydroxymethyl)ethyl>-N^α-(benzyloxycarbonyl)glycinamide 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 19.0h， 以100%的产率得到glycyl-Tris
  参考文献：
  名称：

  甲氨蝶呤-γ-TRIS-脂肪酸偶联物的全合成

  摘要：

  描述了几种区域特异性合成甲氨蝶呤的亲脂性 γ-缀合物的途径。甲氨蝶呤-α-叔丁酯与甘氨酰-TRIS-(单-/二-/三-)棕榈酸酯偶联，然后用三氟乙酸裂解α-保护，得到目标甲氨蝶呤-γ-甘氨酰-TRIS-(单- /di-/tri-) 棕榈酸酯衍生物。制备了甲氨蝶呤-α-苄基-γ-甘氨酰-TRIS-三棕榈酸酯，但没有发现选择性裂解α-酯的方法。最后连接二氨基蝶啶基甲基部分的方法是成功的，但在最后一步中收率低。4-氨基-4-脱氧-N10-甲基蝶酸与谷氨酰-γ-甘氨酰-TRIS-棕榈酸酯衍生物的偶联有效地提供了所需的缀合物。

  DOI：

  10.1071/ch02125

文献信息

• Synthetic Gallic Acid Derivatives as Models for a Comprehensive Study of Antioxidant Activity
  作者：Florence Belin、Philippe Barthélémy、Karine Ruiz、Jean Michel Lacombe、Bernard Pucci

  DOI：10.1002/hlca.200390053

  日期：2003.2

  The synthesis and antioxidant efficiencies of amphiphilic gallic acid derivatives are reported. To specify the impact of chemical structure on the antioxidant efficiency, several structural modifications of gallic acid were performed. The following structural features were chosen: i) introduction of hydrophobic or hydrophilic residues on the gallic acid and the type of their linkage, ii) the hydrophilic

  报道了两亲没食子酸衍生物的合成和抗氧化剂效率。为了说明化学结构对抗氧化剂效率的影响，对没食子酸进行了几种结构修饰。选择了以下结构特征：i）在没食子酸上引入疏水或亲水残基以及它们的连接类型，ii）整个分子的亲水性和/或亲脂性。所制备的不同系列的理化研究表明，该多酚的抗氧化效率明显取决于与亲水和疏水部分的连接性质。始终需要推挽效应，酯或酰胺键似乎很适合提高抗氧化剂的效率。第二，观察到在所施加的氧化条件下，亲水性和/或亲脂性极大地影响了没食子酸衍生物的抗氧化活性。获得的结果与极性悖论相符，疏水性衍生物抑制了水相中的氧化，而亲水性产品则无效。
• Therapeutic compound-fatty acid conjugates
  申请人：Commonwealth Scientific and Industrial Research Organisation

  公开号：US06353124B1

  公开（公告）日：2002-03-05

  The present invention provides therapeutic conjugates which comprise a therapeutic compound bound to one to three acyl groups derived from fatty acids. The therapeutic compounds are preferably non-steroidal anti-infiammatory agents which include a carboxylic acid group. The compounds involve the use of tromethamine or ethanolamine derivative to link the acyl groups derived from fatty acids to the therapeutic compounds.

  本发明提供了治疗性结合物，其中包括一个治疗性化合物与来自脂肪酸的一个至三个酰基结合。这些治疗性化合物通常是非类固醇抗炎药物，包括一个羧酸基团。这些化合物涉及使用醋酸氢三甲胺或乙醇胺衍生物将来自脂肪酸的酰基与治疗性化合物连接起来。
• The use of Tris-Lipidation to modify drug cytotoxicity in multidrug resistant cells expressing P-glycoprotein or MRP1
  作者：Ross A Davey、Mary W Davey、Karen V Cullen、Xanthe E Wells、Craig L Francis、Hua-Ming Williams、Qi Yang、Minoo J Moghaddam、Fred Widmer、Robert G Whittaker

  DOI：10.1038/sj.bjp.0704983

  日期：2002.12

  Increasing the lipophilicity is a strategy often used to improve a compound's cellular uptake and retention but this may also convert it into a substrate for an ATP‐dependent transporter such as P‐glycoprotein or the multidrug resistance‐associated protein (MRP1), which are involved in cellular efflux of drugs. Tris‐Lipidation of compounds is a convenient way of modifying drug lipophilicity and generating an array of derivatives with diverse properties. To determine the effect of Tris‐Lipidation on a drug's cytoxicity in multidrug resistant cells, various glycyl‐Tris‐mono‐ (GTP1), di‐ (GTP2) and tri‐palmitate (GTP3) derivatives were prepared of the cancer chemotherapeutic drugs chlorambucil and methotrexate, and of the anti‐HIV drug AZT. The cytotoxicity of these derivatives and their parent compounds was determined in the CEM/VLB100 cells with increased P‐glycoprotein expression, the CEM/E1000 cells that overexpress MRP1 and the parent, drug‐sensitive CCRF‐CEM cells. Increasing the lipophilicity of AZT increased its cytotoxicity in the sensitive CCRF‐CEM parental cell line while decreased cytotoxicity was observed for the methotrexate derivatives. For the chlorambucil derivatives, both increased (GTP1) and decreased (GTP2) cytotoxicity occurred in the CCRF‐CEM cells. With the exception of AZT‐GTP1, all GTP1 and GTP2 derivatives of chlorambucil, methotrexate and AZT had decreased cytotoxicity in the P‐glycoprotein‐expressing CEM/VLB100 cells while chlorambucil‐GTP1, methotrexate‐GTP2 and methotrexate‐GTP3 were the only compounds with decreased cytotoxicity in the MRP1‐overexpressing CEM/E1000 cells. The number of palmitate residues, the position of derivatisation and the type of linkage all may affect the P‐glycoprotein and MRP1 substrate properties. Tris‐Lipidation may therefore provide a useful way of manipulating the pharmacokinetic properties of drugs. British Journal of Pharmacology (2002) 137, 1280–1286. doi:10.1038/sj.bjp.0704983

  增加疏水性是改善化合物细胞摄取和保留的常见策略，但也可能引发化合物成为ATP依赖性转运蛋白（如P-糖蛋白或多药耐药相关蛋白（MRP1））的底物，这些蛋白参与药物的细胞外排。将化合物进行三酰化是调节药物疏水性的一种简便方法，能够生成一系列具有不同特性的衍生物。 为了研究药物三酰化对多重耐药细胞毒性的影响，制备了抗癌化疗药物卡奇霉素和甲氨蝶呤以及抗HIV药物AZT的甘氨酰-Tris-单（GTP1）、双（GTP2）和三棕榈酰（GTP3）衍生物。在具有P-糖蛋白高表达的CEM/VLB100细胞、MRP1高表达的CEM/E1000细胞及其亲本药物敏感的CCRFR-CEM细胞中，研究了这些衍生物及其母体化合物的细胞毒性。 AZT的疏水性增加提高了其在敏感的CCRFR-CEM亲本细胞系中的细胞毒性，而甲氨蝶呤衍生物的细胞毒性有所降低。对于卡奇霉素衍生物，在CCRFR-CEM细胞中，GTP1增加细胞毒性，GTP2降低。除了AZT-GTP1，所有GTP1和GTP2的卡奇霉素、甲氨蝶呤和AZT衍生物在P-糖蛋白表达的CEM/VLB100细胞中细胞毒性降低，而在MRP1过表达的CEM/E1000细胞中仅有卡奇霉素-GTP1、甲氨蝶呤-GTP2 和甲氨蝶呤-GTP3 的细胞毒性降低。 棕榈酸残基的数量、修饰的位置和连接方式均可能影响P-糖蛋白和MRP1底物特性。 因此，药物的三酰化可能提供一种有效手段，用于调节药物的药代动力学特性。 英国药理学杂志 (2002) 137, 1280–1286。doi:10.1038/sj.bjp.0704983
• TRIANTENNARY CLUSTER GLYCOSIDES, THEIR PREPARATION AND USE
  申请人：RIJKSUNIVERSITEIT LEIDEN

  公开号：EP0655070B1

  公开（公告）日：1998-07-22
• US5885968A
  申请人：——

  公开号：US5885968A

  公开（公告）日：1999-03-23