倍他米松杂质40 | 1881-66-9

• 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: 倍他米松杂质40
• 英文名称: betamethasone 21-methanesulfonate
• 英文别名: Betamethasone 21-mesylate；[2-[(8S,9R,10S,11S,13S,14S,16S,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: 1881-66-9
• 化学式: C₂₃H₃₁FO₇S
• 分子量: 470.559
• InChiKey: ATNWRUJPJUBMHC-DLCSVNPKSA-N

物化性质

• 熔点：
  >174°C (dec.)
• 沸点：
  652.3±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

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

反应信息

• 作为反应物：
  描述：

  倍他米松杂质40 在 lithium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以83 %的产率得到氯倍他索
  参考文献：
  名称：

  抗炎药倍他米松磷酸钠制备新工艺的开发

  摘要：

  在本文中，我们报告了我们为开发一种新型和改进的抗炎类固醇活性药物成分制剂，即倍他米松磷酸钠所做的努力。从市售的倍他米松开始，合成策略包括 C21 位羟基的甲磺酸化，然后是甲磺酸酯衍生物与二叔丁基磷酸钾的关键磷酸化反应，二叔丁基磷酸酯的水解丁酯中间体在弱酸性条件下，最终成盐。开发的工艺使我们能够以 68% 的总收率在多公斤规模下获得所需的倍他米松磷酸钠 ≥ 99.9% HPLC 纯度。还讨论了工艺的成本效益、杂质分析和材料质量。

  DOI：

  10.1021/acs.oprd.2c00329
• 作为产物：
  描述：

  倍他米松 、 甲基磺酰氯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 以99.9 %的产率得到倍他米松杂质40
  参考文献：
  名称：

  抗炎药倍他米松磷酸钠制备新工艺的开发

  摘要：

  在本文中，我们报告了我们为开发一种新型和改进的抗炎类固醇活性药物成分制剂，即倍他米松磷酸钠所做的努力。从市售的倍他米松开始，合成策略包括 C21 位羟基的甲磺酸化，然后是甲磺酸酯衍生物与二叔丁基磷酸钾的关键磷酸化反应，二叔丁基磷酸酯的水解丁酯中间体在弱酸性条件下，最终成盐。开发的工艺使我们能够以 68% 的总收率在多公斤规模下获得所需的倍他米松磷酸钠 ≥ 99.9% HPLC 纯度。还讨论了工艺的成本效益、杂质分析和材料质量。

  DOI：

  10.1021/acs.oprd.2c00329

文献信息

• MILIONI, CATHERINE;EFTHYIMIOPOULOS, CONSTANTIN;KOCH, ETABLI BERNARD;JUNG,+
  作者：MILIONI, CATHERINE、EFTHYIMIOPOULOS, CONSTANTIN、KOCH, ETABLI BERNARD、JUNG,+

  DOI：——

  日期：——
• Channel Expansion in the Ligand-Binding Domain of the Glucocorticoid Receptor Contributes to the Activity of Highly Potent Glucocorticoid Analogues
  作者：Wesley B. Seaton、Susan J. Burke、Alexander R. Fisch、William A. Schilletter、Mary Grace A. Beck、Gabrielle A. Cassagne、Innocence Harvey、Molly S. Fontenot、J. Jason Collier、Shawn R. Campagna

  DOI：10.3390/molecules29071546

  日期：——

  Glucocorticoids (GCs) act through the glucocorticoid receptor (GR) and are commonly used as anti-inflammatory and immunosuppressant medications. Chronic GC use has been linked with unwanted complications such as steroid-induced diabetes mellitus (SIDM), although the mechanisms for these effects are not completely understood. Modification of six GC parent molecules with 2-mercaptobenzothiazole resulted in consistently less promoter activity in transcriptional activation assays using a 3xGRE reporter construct while constantly reducing inflammatory pathway activity. The most selective candidate, DX1, demonstrated a significant reduction (87%) in transactivation compared to commercially available dexamethasone. DX1 also maintained 90% of the anti-inflammatory potential of dexamethasone while simultaneously displaying a reduced toxicity profile. Additionally, two novel and highly potent compounds, DX4 and PN4, were developed and shown to elicit similar mRNA expression at attomolar concentrations that dexamethasone exhibits at nanomolar dosages. To further explain these results, Molecular Dynamic (MD) simulations were performed to examine structural changes in the ligand-binding domain of the glucocorticoid receptor in response to docking with the top ligands. Differing interactions with the transcriptional activation function 2 (AF-2) region of the GR may be responsible for lower transactivation capacity in DX1. DX4 and PN4 lose contact with Arg611 due to a key interaction changing from a stronger hydrophilic to a weaker hydrophobic one, which leads to the formation of an unoccupied channel at the location of the deacylcortivazol (DAC)-expanded binding pocket. These findings provide insights into the structure–function relationships important for regulating anti-inflammatory activity, which has implications for clinical utility.