地塞米松 21-甲磺酸酯 | 2265-22-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 地塞米松 21-甲磺酸酯
• 中文别名: 地塞米松21-甲磺酸酯；9Α-氟-11Β,17Α-二羟基-16Α-甲基-21-甲磺酰氧基孕甾-1,4-二烯-3,20-二酮
• 英文名称: Dexamethasone 21-mesylate
• 英文别名: 2-[(1R,2S,10S,11S,13R,14R,15S,17S)-1-fluoro-14,17-dihydroxy-2,13,15-trimethyl-5-oxotetracyclo[8.7.0.0²'⁷.0^11,15]heptadeca-3,6-dien-14-yl]-2-oxoethyl methanesulfonate；methanesulfonic acid 2-(9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl ester；dexamethasone-21-mesylate；dexamethasone mesylate；dexmethasone mesylate；Dexamethasone 21-methanesulfonate；[2-[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] methanesulfonate
• CAS: 2265-22-7
• 化学式: C₂₃H₃₁FO₇S
• 分子量: 470.559
• InChiKey: ATNWRUJPJUBMHC-HOGMHMTRSA-N

物化性质

• 沸点：
  652.3±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、甲醇（微溶、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• 储存条件：
  -20°C，密封保存，置于干燥处。

制备方法与用途

用途：用于制取地塞米松磷酸钠。

反应信息

• 作为反应物：
  描述：

  地塞米松 21-甲磺酸酯 在 三乙胺 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 4.0h， 生成 [2-[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] 3-[[3-[2-[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-3-oxo-2-(phenylmethoxycarbonylamino)propyl]disulfanyl]-2-(phenylmethoxycarbonylamino)propanoate
  参考文献：
  名称：

  Synthesis of new local anti-inflammatory thiosteroids based on antedrug concept

  摘要：

  The synthesis and the in vitro pharmacological evaluation of a number of topical corticosteroid derivatives designed on the basis of the antedrug concept are reported. Three series of compounds were synthesized in which sulfur-containing amino acids were incorporated to the steroidal structure in the 21 position. Compounds of series I are diesters of cystine with the 21-hydroxyl groups of the corticosteroids, while series II and III contain 21-amino and 21-thio corticosteroid derivatives, respectively. The new compounds were less potent than the parent corticosteroids in vitro. The 21-yl-[9-alpha-fluoro-11-beta,17-alpha-dihydroxy-16-alpha-methyl-1,4-pregnadiene-3,20-dione]-S-acetylamino cysteine 13 was the most interesting compound of the series and is now under further evaluation.

  DOI：

  10.1016/0223-5234(91)90137-c
• 作为产物：
  描述：

  地塞米松 、 甲基磺酰氯 在 吡啶 作用下， 反应 17.0h， 以83%的产率得到地塞米松 21-甲磺酸酯
  参考文献：
  名称：

  [EN] METHODS FOR EFFICIENT DELIVERY OF THERAPEUTIC MOLECULES IN VITRO AND IN VIVO
  [FR] PROCÉDÉS D'ADMINISTRATION EFFICACE DE MOLÉCULES THÉRAPEUTIQUES IN VITRO ET IN VIVO

  摘要：

  本文描述了一种用于在哺乳动物内耳多种细胞类型中直接传递蛋白质的组合物。这些组合物可用于传递蛋白质（如基因编辑因子），以编辑与耳聋或相关疾病相关的遗传突变。传递基因组编辑蛋白质以编辑和纠正遗传突变，可保护或恢复遗传性耳聋的听力。治疗方法包括将这些分子进行胞内传递，以达到特定的治疗目标。

  公开号：

  WO2016069910A1

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS AND METHODS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES ET MÉTHODES
  申请人：POP TEST ONCOLOGY LLC

  公开号：WO2017023694A1

  公开（公告）日：2017-02-09

  This invention relates the use of Cortisol blockers (e.g., glucocorticoid receptor [GR] antagonists) for the treating or preventing viral infections, treating or preventing treatment resistant prostate cancer, treating or preventing neoplasia, and treating or preventing infection related to acute or chronic injury or disease.

  本发明涉及使用皮质醇阻断剂（例如，糖皮质激素受体[GR]拮抗剂）用于治疗或预防病毒感染，治疗或预防难治性前列腺癌，治疗或预防肿瘤，以及治疗或预防与急性或慢性损伤或疾病相关的感染。
• Dexamethasone 21-(.beta.-isothiocyanatoethyl)thio ether: a new affinity label for glucocorticoid receptors
  作者：Susana Lopez、S. Stoney Simons

  DOI：10.1021/jm00110a002

  日期：1991.6

  SDS-polyacrylamide gels, only one specifically labeled species at 98 kDa, which is the molecular weight of authentic rat glucocorticoid receptor. These data directly establish Dex-NCS as a new affinity label for glucocorticoid receptors. Data on the reactivity of Dex-NCS and the stability of [3H]Dex-NCS-labeled receptors suggest that a cysteine SH group has been labeled.

  合成的糖皮质激素地塞米松（Dex）的C-21甲磺酸酯是糖皮质激素受体的有效亲电标签，并具有不可逆的抗糖皮质激素活性。为了获得具有不同生物活性的其他亲和标记类固醇，制备了几种新的Dex衍生物，它们在距C-21位置不同的距离处含有一个反应性亲电子取代基。在无细胞竞争试验中，所有化合物对大鼠糖皮质激素受体的亲和力都较低（小于或等于Dex的8％）。然而，一种化合物地塞米松21-（β-异硫氰酸根合乙基）硫醚（Dex-NCS）由于具有阻断[3H] Dex的无细胞交换结合的能力而显得是亲和标记。[3H] Dex-NCS如此合成，并与无细胞受体反应，经过变性的SDS-聚丙烯酰胺凝胶分析后，仅得到一种在98 kDa处特异性标记的物种，即真正的大鼠糖皮质激素受体的分子量。这些数据直接将Dex-NCS确立为糖皮质激素受体的新亲和标记。关于Dex-NCS的反应性和[3H] Dex-NCS标记的受体的稳定性的数据表明，半胱氨酸SH基团已经被标记。
• Novel Cationic Lipids with Enhanced Gene Delivery and Antimicrobial Activity
  作者：David E. Fein、Robert Bucki、Fitzroy Byfield、Katarzyna Leszczynska、Paul A. Janmey、Scott L. Diamond

  DOI：10.1124/mol.110.066670

  日期：2010.9

  Cationic lipids facilitate plasmid delivery, and some cationic sterol-based compounds have antimicrobial activity because of their amphiphilic character. These dual functions are relevant in the context of local ongoing infection during intrapulmonary gene transfer for cystic fibrosis. The transfection activities of two cationic lipids, dexamethasone spermine (DS) and disubstituted spermine (D2S), were tested as individual components and mixtures in bovine aortic endothelial cells and A549 cells. The results showed a 3- to 7-fold improvement in transgene expression for mixtures of DS with 20 to 40 mol% D2S. D2S and coformulations with DS, dioleoyl phosphatidylethanolamine, and DNA exhibited potent bactericidal activity against Escherichia coli MG1655, Bacillus subtilis , and Pseudomonas aeruginosa PAO1, which was maintained in bronchoalveolar lavage fluid. Complete bacterial killing was demonstrated at ∼5 μM, including gene delivery formulations, with 2 orders of magnitude higher tolerance before eukaryotic membrane disruption (erythrocyte hemolysis). D2S also exhibited lipopolysaccharide (LPS) scavenging activity resulting in significant inhibition of LPS-mediated activation of human neutrophils with 85 and 65% lower interleukin-8 released at 12 and 24 h, respectively. Mixtures of DS and D2S can improve transfection activity over common lipofection reagents, and D2S has strong antimicrobial action suited for the suppression of bacterial-mediated inflammation.

  阳离子脂质可促进质粒的传递，而一些阳离子甾醇类化合物因其两亲性而具有抗菌活性。在治疗囊性纤维化的肺内基因转移过程中，这些双重功能与局部持续感染有关。研究人员测试了地塞米松精胺（DS）和二取代精胺（D2S）这两种阳离子脂作为单独成分和混合物在牛主动脉内皮细胞和 A549 细胞中的转染活性。结果表明，DS 与 20-40 mol% D2S 的混合物的转基因表达量提高了 3-7 倍。D2S 以及与 DS、二油酰磷脂酰乙醇胺和 DNA 的复配物对大肠杆菌 MG1655、枯草杆菌和铜绿假单胞菌 PAO1（在支气管肺泡灌洗液中培养）具有很强的杀菌活性。包括基因递送制剂在内，在 5 μM 以下就能完全杀死细菌，在真核生物膜破坏（红细胞溶血）之前的耐受性要高出 2 个数量级。D2S 还具有清除脂多糖（LPS）的活性，可显著抑制 LPS 介导的人中性粒细胞活化，12 小时和 24 小时释放的白细胞介素-8 分别减少 85% 和 65%。与普通脂质感染试剂相比，DS 和 D2S 的混合物可提高转染活性，D2S 具有很强的抗菌作用，适用于抑制细菌介导的炎症。
• Preparation of Dexamethasone-Based Cationic Liposome and Its Application to Gene Delivery <i>In Vitro</i>
  作者：Tae-Hun Kim、Gwang Sig Yu、Hye Choi、Young Jung Shim、Minhyung Lee、Joon Sig Choi

  DOI：10.1166/jnn.2011.3407

  日期：2011.2.1

  In this study, dexamethasone was conjugated to PAMAM dendrimer (generation 0) and its gene transfection efficiency was investigated. To make a liposomal solution for gene delivery, DOPE was used as a fusogenic helper lipid. In gel retardation assay, PAMAM-dexamethasone conjugate (PAM-Dex)/DOPE liposome/DNA complex was completely retarded at 8:1 N/P (nitrogen/phosphate) ratio. The physicochemical characteristics are studied by measuring the average size distribution and ζ-potential values of the complexes. In vitro transfection assay showed that the PAM-Dex/DOPE liposome/DNA complex displayed higher gene delivery efficiency compared to PAMAM/DNA complex. In addition, PAM-Dex/DOPE liposome showed the lowest toxicity compared to PAMAM, PEI 25 kD and Lipofectamine. These results indicate that PAM-Dex/DOPE liposome has a potential to be used as an efficient gene carrier for gene therapy.

  本研究将地塞米松与 PAMAM 树枝状聚合物（第 0 代）共轭，并对其基因转染效率进行了研究。为了制作用于基因递送的脂质体溶液，使用了 DOPE 作为助熔脂。在凝胶延缓试验中，PAMAM-地塞米松共轭物（PAM-Dex）/DOPE 脂质体/DNA 复合物在 8:1 N/P（氮/磷酸盐）比时完全延缓。通过测量复合物的平均粒度分布和ζ电位值，对其理化特性进行了研究。体外转染试验表明，与 PAMAM/DNA 复合物相比，PAM-Dex/DOPE 脂质体/DNA 复合物的基因递送效率更高。此外，与 PAMAM、PEI 25 kD 和 LipofectAMine 相比，PAM-Dex/DOPE 脂质体的毒性最低。这些结果表明，PAM-Dex/DOPE 脂质体有望用作基因治疗的高效基因载体。
• Synthesis and use of reagents for improved DNA lipofection and/or slow release prodrug and drug therapies
  申请人：Diamond L. Scott

  公开号：US20050069577A1

  公开（公告）日：2005-03-31

  The invention relates to compositions and methods for a one-step synthetic technique for making cationic steroid or cationic drug molecules for use as delivery vehicles. The invention further relates to methods for using cationic steroid molecules in lipofection or transfection, delivery of drugs, and for treatment of inflammation and other diseases and disorders. The invention also relates to cationic steroid prodrugs and cationic prodrugs and to methods of modifying drugs.

  本发明涉及一种用于制备阳离子类固醇或阳离子类药物分子的一步合成技术的组合物和方法，用作传递载体。该发明还涉及使用阳离子类固醇分子进行脂质体转染或转染、药物传递以及治疗炎症和其他疾病和障碍的方法。该发明还涉及阳离子类固醇前药和阳离子前药以及修改药物的方法。