(2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-((1,3-dioxoisoindolin-2-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 390756-32-8

• 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: (2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-((1,3-dioxoisoindolin-2-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• 英文别名: [(2R,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-(1,3-dioxoisoindol-2-yl)oxyoxan-2-yl]methyl acetate
• CAS: 390756-32-8
• 化学式: C₂₂H₂₃NO₁₂
• 分子量: 493.424
• InChiKey: HZSCKBDHKVEXLR-IHZGOTPNSA-N

物化性质

• 沸点：
  576.9±60.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  161
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-((1,3-dioxoisoindolin-2-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 甲基肼 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 O-(β-D-galactopyranosyl)hydroxylamine
  参考文献：
  名称：

  Expedient synthesis of aminooxylated-carbohydrates for chemoselective access of glycoconjugates

  摘要：

  Herein, we describe an efficient preparation of various biologically important carbohydrate motifs bearing an aminooxy group at the anomeric position. These nucleophilic sugar analogues represent useful intermediates for the chemoselective preparation of glycoconjugates. The key glycosylation step involves the coupling of fluoro-activated protected sugar and N-hydroxyphthalimide in the presence of BF3. Et2O. Final deprotection and cleavage of the phthalimide moiety with methylhydrazine afforded new Glc-beta -ONH2 3, GalNAc-beta -ONH2 9, Glc-alpha -ONH2 14, Gal-alpha -ONH2 17 and Man-alpha -ONH2 20 derivatives with good yields. Compared to the literature results, the preparation of Gal-beta -ONH2 6, GalNAc-alpha -ONH2 11 and Lac-beta -ONH2 23 proved to be more efficient. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01614-8
• 作为产物：
  描述：

  N-羟基邻苯二甲酰亚胺 、 2,3,4,6-四乙酰氧基-alpha-D-吡喃糖溴化物 在 四丁基硫酸氢铵 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以80%的产率得到(2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-((1,3-dioxoisoindolin-2-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  Expedient synthesis of aminooxylated-carbohydrates for chemoselective access of glycoconjugates

  摘要：

  Herein, we describe an efficient preparation of various biologically important carbohydrate motifs bearing an aminooxy group at the anomeric position. These nucleophilic sugar analogues represent useful intermediates for the chemoselective preparation of glycoconjugates. The key glycosylation step involves the coupling of fluoro-activated protected sugar and N-hydroxyphthalimide in the presence of BF3. Et2O. Final deprotection and cleavage of the phthalimide moiety with methylhydrazine afforded new Glc-beta -ONH2 3, GalNAc-beta -ONH2 9, Glc-alpha -ONH2 14, Gal-alpha -ONH2 17 and Man-alpha -ONH2 20 derivatives with good yields. Compared to the literature results, the preparation of Gal-beta -ONH2 6, GalNAc-alpha -ONH2 11 and Lac-beta -ONH2 23 proved to be more efficient. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01614-8

文献信息

• Prodrug design for the potent cardiovascular agent Nω-hydroxy-l-arginine (NOHA): Synthetic approaches and physicochemical characterization
  作者：Dennis Schade、Jürke Kotthaus、Nikola Klein、Joscha Kotthaus、Bernd Clement

  DOI：10.1039/c0ob01117g

  日期：——

  N ω-Hydroxy-L-arginine (NOHA)—the physiological nitric oxide precursor—is the intermediate of NO synthase (NOS) catalysis. Besides the important fact of releasing NO mainly at the NOS-side of action, NOHA also represents a potent inhibitor of arginases, making it an ideal therapeutic tool to treat cardiovascular diseases that are associated with endothelial dysfunction. Here, we describe an approach to impart NOHA drug-like properties, particularly by wrapping up the chemically and metabolically instable N-hydroxyguanidine moiety with different prodrug groups. We present synthetic routes that deliver several more or less highly substituted NOHA derivatives in excellent yields. Versatile prodrug strategies were realized, including novel concepts of bioactivation. Prodrug candidates were primarily investigated regarding their hydrolytic and oxidative stabilities. Within the scope of this work, we essentially present the first prodrug approaches for an interesting pharmacophoric moiety, i.e., N-hydroxyguanidine.

  N-羟基-L-精氨酸（NOHA）——生理性一氧化氮前体——是NO合酶（NOS）催化的中间产物。除了在NOS作用侧主要释放NO这一重要事实外，NOHA还是一种强效的精氨酸酶抑制剂，使其成为治疗与内皮功能障碍相关的心血管疾病的理想治疗工具。在这里，我们描述了一种赋予NOHA药物样特性的途径，特别是通过用不同的前药基团包裹化学和代谢不稳定的N-羟基鸟嘌呤部分。我们展示了几种合成途径，以优良的产率获得几种多或少高度取代的NOHA衍生物。实现了多功能的前药策略，包括生物活化的新概念。前药候选物主要针对其水解和氧化稳定性进行了研究。在本工作范围内，我们基本上展示了针对一个有趣的药效团部分，即N-羟基鸟嘌呤的第一个前药策略。
• β-Galactosidase-activated nitroxyl (HNO) donors provide insights into redox cross-talk in senescent cells
  作者：Laxman R. Sawase、T. Anand Kumar、Abraham B. Mathew、Vinayak S. Khodade、John P. Toscano、Deepak K. Saini、Harinath Chakrapani

  DOI：10.1039/d3cc03094f

  日期：——

  A probe that generates nitroxyl (HNO) reveals the influence of redox cross-talk in cells.

  一种能生成硝基（HNO）的探针揭示了细胞中氧化还原交叉作用的影响。
• Senolytic compositions and uses thereof
  申请人：Rubedo Life Sciences, Inc.

  公开号：US11026963B2

  公开（公告）日：2021-06-08

  Provided herein are senolytic agents for selectively killing senescent cells that are associated with numerous pathologies and diseases, including age-related pathologies and diseases. As disclosed herein, senescent cell-associated diseases and disorders may be treated or prevented by administering at least one senolytic agent or pharmaceutical compositions thereof. The senescent cell-associated diseases or disorders treated or prevented by the methods described herein include, but are not limited to, cardiovascular diseases or disorders, cardiovascular diseases and disorders associated with arteriosclerosis, such as atherosclerosis, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), osteoarthritis, inflammatory diseases or disorders, autoimmune diseases or disorders, pulmonary diseases or disorders, neurological diseases or disorders, dermatological diseases or disorders, chemotherapeutic side effects, radiotherapy side effects, metastasis and metabolic diseases.

  本文提供了用于选择性杀死衰老细胞的衰老剂，衰老细胞与多种病理和疾病有关，包括与年龄有关的病理和疾病。如本文所述，衰老细胞相关疾病可通过施用至少一种衰老分解剂或其药物组合物来治疗或预防。本文所述方法可治疗或预防的衰老细胞相关疾病或紊乱包括但不限于心血管疾病或紊乱、与动脉硬化相关的心血管疾病和紊乱，如动脉粥样硬化、特发性肺纤维化（IPF）、慢性阻塞性肺病（COPD）、骨关节炎、炎症性疾病或紊乱、自身免疫性疾病或紊乱、肺部疾病或紊乱、神经系统疾病或紊乱、皮肤病或紊乱、化疗副作用、放疗副作用、转移和代谢性疾病。
• Synthesis and biological evaluation of the suberoylanilide hydroxamic acid (SAHA) β-glucuronide and β-galactoside for application in selective prodrug chemotherapy
  作者：Mickaël Thomas、Freddy Rivault、Isabelle Tranoy-Opalinski、Joëlle Roche、Jean-Pierre Gesson、Sébastien Papot

  DOI：10.1016/j.bmcl.2006.11.042

  日期：2007.2

  The beta-O-glucuronide and beta-O-galactoside of SAHA have been prepared and evaluated as prodrugs for selective cancer chemotherapy (ADEPT, PMT). These new compounds are stable under physiological conditions and do not exhibit any antiproliferative activity compared to the parent drug after a 48-h treatment of H661 cells. The glucuronide derivative did not lead to the release of the drug in the presence of either Escherichia coli or bovine liver beta-glucuronidase. On the other hand, under enzymatic cleavage of galactoside prodrug by the corresponding enzyme, a rapid release of SARA was observed demonstrating that the beta-O-galactoside of SAHA is a promising candidate for in vivo investigations. (c) 2006 Elsevier Ltd. All rights reserved.
• WO2020014409A5
  申请人：——

  公开号：WO2020014409A5

  公开（公告）日：2022-07-19