3-amino-5-[(1,3,4,5-tetraacetoxycyclohexanecarbonyl)amino]benzoic acid methyl ester | 859224-90-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-amino-5-[(1,3,4,5-tetraacetoxycyclohexanecarbonyl)amino]benzoic acid methyl ester
• 英文别名: (1R,2S,3R,5S)-5-((3-amino-5-(methoxycarbonyl)phenyl)carbamoyl)cyclohexane-1,2,3,5-tetrayltetraacetate；5-((3-amino-5-(methoxycarbonyl)phenyl)carbamoyl)cyclohexane-1,2,3,5-tetrayltetraacetate
• CAS: 859224-90-1
• 化学式: C₂₃H₂₈N₂O₁₁
• 分子量: 508.482
• InChiKey: AUYUELBKJQACAG-URFJDIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.88
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  186.62
• 氢给体数：
  2.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  3-amino-5-[(1,3,4,5-tetraacetoxycyclohexanecarbonyl)amino]benzoic acid methyl ester 在 lithium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 16.25h， 生成 3-[(1-benzothien-2-ylcarbonyl)amino]-5-({[(3R,5R)-1,3,4,5-tetrahydroxycyclohexyl]carbonyl}amino)benzoic acid
  参考文献：
  名称：

  Quinic Acid Derivatives as Sialyl Lewis^x-Mimicking Selectin Inhibitors:  Design, Synthesis, and Crystal Structure in Complex with E-Selectin

  摘要：

  A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.

  DOI：

  10.1021/jm050049l
• 作为产物：
  描述：

  (1R,3R,4R,5R)-(-)-quinic acid tetraacetate 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-amino-5-[(1,3,4,5-tetraacetoxycyclohexanecarbonyl)amino]benzoic acid methyl ester
  参考文献：
  名称：

  Quinic Acid Derivatives as Sialyl Lewis^x-Mimicking Selectin Inhibitors:  Design, Synthesis, and Crystal Structure in Complex with E-Selectin

  摘要：

  A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.

  DOI：

  10.1021/jm050049l

文献信息

• [EN] QUINIC ACID-MODIFIED NANOPARTICLES AND USES THEREOF<br/>[FR] NANOPARTICULES MODIFIÉES PAR ACIDE QUINIQUE ET UTILISATIONS ASSOCIÉES
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2018208700A1

  公开（公告）日：2018-11-15

  The present invention generally relates to targeted nanoparticle delivery to E-selectin- or P-selectin-positive cells or tissues. In particular, this invention discloses a method for preparing quinic acid-modified nanoparticles for targeted drug delivery to cancerous cells or tissues via E-selectin- or P-selectin-mediated transcytosis. The invention described herein also pertains to pharmaceutical compositions and methods for treating cancers.

  本发明通常涉及针对E-选择素或P-选择素阳性细胞或组织的靶向纳米粒子输送。特别地，本发明揭示了一种制备奎尼酸修饰纳米粒子用于通过E-选择素或P-选择素介导的横穿作用靶向输送药物到癌细胞或组织的方法。本发明还涉及用于治疗癌症的制药组合物和方法。
• Quinic Acid‐Conjugated Nanoparticles Enhance Drug Delivery to Solid Tumors via Interactions with Endothelial Selectins
  作者：Jun Xu、Steve Seung‐Young Lee、Howon Seo、Liang Pang、Yearin Jun、Ruo‐Yu Zhang、Zhong‐Yin Zhang、Pilhan Kim、Wooin Lee、Stephen J. Kron、Yoon Yeo

  DOI：10.1002/smll.201803601

  日期：2018.12

  drug delivery to tumors, poly(lactic‐co‐glycolic acid) (PLGA) NPs are modified with a quinic acid (QA) derivative, synthetic mimic of selectin ligands. QA‐decorated NPs (QA‐NP) interact with human umbilical vein endothelial cells expressing E‐/P‐selectins and induce transient increase in endothelial permeability to translocate across the layer. QA‐NP reach selectin‐upregulated tumors, achieving greater

  当前的纳米颗粒（NP）药物载体主要依赖于增强的渗透性和保留（EPR）效应，用于选择性地将药物递送至实体瘤。然而，在没有持续的 EPR 效应的情况下，瘤周内皮细胞可以作为肿瘤的进入屏障并对 NPs 的有效性产生负面影响。鉴于肿瘤周围内皮是向肿瘤输送药物的潜在屏障，聚乳酸-共-乙醇酸 (PLGA) NPs 用奎尼酸 (QA) 衍生物进行修饰，该衍生物是选择素配体的合成模拟物。QA-decorated NPs (QA-NP) 与表达 E-/P-选择素的人脐静脉内皮细胞相互作用，并诱导内皮通透性瞬时增加以跨层转移。QA-NP 到达选择素上调的肿瘤，与聚乙二醇修饰的 NPs (PEG-NP) 相比，实现了更大的肿瘤积累和紫杉醇 (PTX) 递送。在不同的动物模型和给药方案中，在相同的 PTX 剂量下，负载 PTX 的 QA-NP 显示出比紫杉醇或负载 PTX 的 PEG-NP 更高的抗癌功效。在 40-60%