9α-fluoro-11β-hydroxy-17β-<(methylthio)carbonyl>-17α-(propionyloxy)-16β-methylandrosta-1,4-dien-3-one | 79578-08-8

• 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-17β-<(methylthio)carbonyl>-17α-(propionyloxy)-16β-methylandrosta-1,4-dien-3-one
• 英文别名: S-methyl 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carbothioate；9α-fluoro-11β-hydroxy-17β-[(methylthio)carbonyl]-17α-(propionyloxy)-16β-methylandrosta-1,4-dien-3-one；[(8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro-11-hydroxy-10,13,16-trimethyl-17-methylsulfanylcarbonyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] propanoate
• CAS: 79578-08-8
• 化学式: C₂₅H₃₃FO₅S
• 分子量: 464.598
• InChiKey: RIOLVARIMDVNCD-XGQKBEPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 碳酸氢钠 、 二乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 4.0h， 生成 9α-fluoro-11β-hydroxy-17β-<(methylthio)carbonyl>-17α-(propionyloxy)-16β-methylandrosta-1,4-dien-3-one
  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

文献信息

• Thiol esters from steroid 17.beta.-carboxylic acids: carboxylate activation and internal participation by 17.alpha.-acylates
  作者：Denis J. Kertesz、Michael Marx

  DOI：10.1021/jo00362a028

  日期：1986.6
• EDWARDS, J. A.
  作者：EDWARDS, J. A.

  DOI：——

  日期：——