9α-Fluoro-11β-hydroxy-16-methylene-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carboxylic acid | 52625-28-2

• 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
• 英文名称: 9α-Fluoro-11β-hydroxy-16-methylene-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carboxylic acid
• 英文别名: 9α-fluoro-11β-hydroxy-16-methylene-17α-(propionyloxy)androsta-1,4-diene-17β-carboxylic acid；(8S,9R,10S,11S,13S,14S,17R)-9-fluoro-11-hydroxy-10,13-dimethyl-16-methylidene-3-oxo-17-propanoyloxy-7,8,11,12,14,15-hexahydro-6H-cyclopenta[a]phenanthrene-17-carboxylic acid
• CAS: 52625-28-2
• 化学式: C₂₄H₂₉FO₆
• 分子量: 432.489
• InChiKey: GYDBQUZEJDXCLP-VTFYZQLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9α-Fluoro-11β-hydroxy-16-methylene-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carboxylic acid 在 silver fluoride 、 碳酸氢钠 、 二乙胺 、 三乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 丙酮 、 乙腈 为溶剂， 反应 2.0h， 生成 S-fluoromethyl 9α-fluoro-11β-hydroxy-16-methylene-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carbothioate
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships in a Series of Antiinflammatory Corticosteroid Analogs, Halomethyl Androstane-17.beta.-carbothioates and -17.beta.-carboselenoates

  摘要：

  The preparation and topical antiinflammatory potencies of a series of halomethyl 17 alpha-(acyloxy)11 beta-hydroxy-3 -oxoandrosta-1,4-diene-17 beta-carbothioates, carrying combinations of 6 alpha-fluoro, 9 alpha-fluoro, 16-methyl, and 16-methylene substituents, are described. Key synthetic stages were the preparation of carbothioic acids and their reaction with dihalomethanes. The carbothioic acids were formed from 17 beta-carboxylic acids by initial reaction with dimethylthiocarbamoyl chloride followed by aminolysis of the resulting rearranged mixed anhydride with diethylamine, or by carboxyl activation with 1,1'-carbonyldiimidazole (CDI) or 2-fluoro-N-methylpyridinium tosylate (FMPT) and reaction with hydrogen sulfide, the choice of reagent being governed by the 17 alpha-substituent. Carboxyl activation with FMPT and reaction with sodium hydrogen selenide led to the halomethyl 16-methyleneandrostane-17 beta-carboselenoat analogues. Antiinflammatory potencies were measured in humans using the vasoconstriction assay and in rats and mice by a modification the Tonelli croton oil ear assay. Best activities were shown by fluoromethyl and chloromethyl carbothioates with a 17 alpha-propionyloxy group. S-Fluoromethyl 6(alpha,9 alpha-difluoro-11 beta-hydroxy-16 alpha-methyl-3-oxo-17 alpha-(propionyloxy)androsta-1,4-diene-17 beta-carbothioate (fluticasone propionate, FP) was selected for clinical study as it showed high topical antiinflammatory activity but caused little hypothalamic-pituitary-adrenal suppression after topical or oral administration to rodents.

  DOI：

  10.1021/jm00048a008
• 作为产物：
  描述：

  在 二乙胺 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 9α-Fluoro-11β-hydroxy-16-methylene-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carboxylic acid
  参考文献：
  名称：

  Novel glucocorticoid antedrugs possessing a C16,17-fused γ-lactone ring

  摘要：

  制备了一系列在 9δ-氟-11δ²-羟基-3-氧代雄甾烷-1,4-二烯核的 16δ²、17δ² 位上融合并在 16δ±、17δ± 位上具有氧取代基的新型 δ³ 丁内酯，并将其作为糖皮质激素激动剂进行了测试。还对这些化合物在人体血浆中的稳定性进行了测试。结果发现，内酯 5 在血浆中会迅速水解，而衍生物 18 则是一种强效的糖皮质激素激动剂，但在血浆中很稳定。X 射线衍射研究证实了化合物 18 的 C21S 非对映异构体的结构。

  DOI：

  10.1039/a908358h