dibenzyl (2S)-2-[3-[(2-aminoacetyl)-[3-[[(2S)-1,4-dioxo-1,4-bis(phenylmethoxy)butan-2-yl]amino]-3-oxopropyl]amino]propanoylamino]butanedioate | 1372688-64-6

• 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: dibenzyl (2S)-2-[3-[(2-aminoacetyl)-[3-[[(2S)-1,4-dioxo-1,4-bis(phenylmethoxy)butan-2-yl]amino]-3-oxopropyl]amino]propanoylamino]butanedioate
• CAS: 1372688-64-6
• 化学式: C₄₄H₄₈N₄O₁₁
• 分子量: 808.885
• InChiKey: WPRVUGNJBOSASS-BCRBLDSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  59
• 可旋转键数：
  27
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  210
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-(2-(2-(2-(((3R,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)ethoxy)ethoxy)ethoxy)acetic acid 、 dibenzyl (2S)-2-[3-[(2-aminoacetyl)-[3-[[(2S)-1,4-dioxo-1,4-bis(phenylmethoxy)butan-2-yl]amino]-3-oxopropyl]amino]propanoylamino]butanedioate 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 为溶剂， 反应 15.33h， 以78%的产率得到
  参考文献：
  名称：

  Design, synthesis and evaluation of liposomes modified with dendritic aspartic acid for bone-specific targeting

  摘要：

  Bone diseases are notoriously difficult diseases to treat due to the comparatively low blood flows in bone tissue. Therefore, targeting delivery of drugs to bone may not only enhance the treatment efficacy, but also reduce the quantity of drug administered. In order to increase the distribution of paclitaxel (PTX) in bone, in this study, a series of novel dendritic aspartic acid derivatives were designed and synthesized as liposome ligands to deliver PTX to bone effectively. The liposomes were prepared by thin film hydration method and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis were also characterized. All the aspartic acid-coated liposomes showed more than 60% binding rates to hydroxyapatite (HAP), especially the PTX-Asp(8)-Lip exhibited dramatic binding rates (> 97%) after 24 h. Moreover, the bone-targeting study in vivo indicated that all liposomes could improve the accumulation of PTX in bone, among which, the PTX-Asp(8)-Lip showed the best affinity due to the increase of aspartic acid residues exposed on the liposome surface. These results provided a novel and effective entry to the development of bone-targeting drugs.

  DOI：

  10.1016/j.chemphyslip.2019.104832
• 作为产物：
  描述：

  3-[苄基-(2-乙氧基羰基乙基)-氨基]-丙酸乙酯 在 palladium on activated charcoal 、 甲酸铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 dibenzyl (2S)-2-[3-[(2-aminoacetyl)-[3-[[(2S)-1,4-dioxo-1,4-bis(phenylmethoxy)butan-2-yl]amino]-3-oxopropyl]amino]propanoylamino]butanedioate
  参考文献：
  名称：

  Design, synthesis and evaluation of liposomes modified with dendritic aspartic acid for bone-specific targeting

  摘要：

  Bone diseases are notoriously difficult diseases to treat due to the comparatively low blood flows in bone tissue. Therefore, targeting delivery of drugs to bone may not only enhance the treatment efficacy, but also reduce the quantity of drug administered. In order to increase the distribution of paclitaxel (PTX) in bone, in this study, a series of novel dendritic aspartic acid derivatives were designed and synthesized as liposome ligands to deliver PTX to bone effectively. The liposomes were prepared by thin film hydration method and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis were also characterized. All the aspartic acid-coated liposomes showed more than 60% binding rates to hydroxyapatite (HAP), especially the PTX-Asp(8)-Lip exhibited dramatic binding rates (> 97%) after 24 h. Moreover, the bone-targeting study in vivo indicated that all liposomes could improve the accumulation of PTX in bone, among which, the PTX-Asp(8)-Lip showed the best affinity due to the increase of aspartic acid residues exposed on the liposome surface. These results provided a novel and effective entry to the development of bone-targeting drugs.

  DOI：

  10.1016/j.chemphyslip.2019.104832

文献信息

• Design and synthesis of novel amphiphilic Janus dendrimers for bone-targeted drug delivery
  作者：Junzhu Pan、Min Wen、Dongqin Yin、Bo Jiang、Dongsheng He、Li Guo

  DOI：10.1016/j.tet.2012.02.040

  日期：2012.4

  paper, we synthesized a range of amphiphilic Janus dendrimers, which consisted of acidic amino acid and naproxen molecules as the peripheral groups, as novel potential bone-targeting dendritic drug delivery. These dendrimers take advantage of a dendritic display to carry multiple drug molecules and targeting moieties simultaneously. All of the dendrimers exhibited more than 80% binding rates to hydroxyapatite

  在本文中，我们合成了一系列由酸性氨基酸和萘普生分子作为外围基团的两亲性Janus树状大分子，作为新型潜在的靶向骨的树突状药物递送。这些树枝状聚合物利用树枝状展示来同时携带多个药物分子和靶向部分。所有的树枝状聚合物均显示出与羟基磷灰石（HAP）的结合率超过80％，特别是[G 2 ]树枝状聚合物（2a和2b）显示出显着的结合率（> 95％）。此外，树突状药物递送系统显着提高了萘普生的溶解度，尤其是萘普生的浓度2b达到5.37 mg / ml，是天然药物的28倍以上。此外，细胞活力研究表明，所有树状聚合物均未表现出对HEK293细胞的明显细胞毒性。这些结果为新型靶向骨的药物的开发提供了有效的入口。
• Synthesis and evaluation of novel bone-targeting ibuprofen prodrug based on dendritic aspartic acid
  作者：Yi Zhao、Ze Zhao、Yamin Cui、Changqing Chen、Changwei Xie、Yang Yang

  DOI：10.32383/appdr/137902

  日期：2021.8.27