17α-acetoxy-9α-fluoro-11β-hydroxy-16β-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid | 37927-21-2

• 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: 17α-acetoxy-9α-fluoro-11β-hydroxy-16β-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid
• 英文别名: 17α-acetoxy-9α-fluoro-11β-hydroxy-16β-methylandrosta-1,4-diene-17β-carboxylic acid；(8S,9R,10S,11S,13S,14S,16S,17R)-17-acetyloxy-9-fluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carboxylic acid
• CAS: 37927-21-2
• 化学式: C₂₃H₂₉FO₆
• 分子量: 420.478
• InChiKey: CMOYCXHQVNWCLN-ZPXFZMPLSA-N

物化性质

• 沸点：
  566.6±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 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：

  17α-acetoxy-9α-fluoro-11β-hydroxy-16β-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid 在 TEA 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 11β,17α-dihydroxy-9α-fluoro-16β-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid 17,20-(1'-methyl-1'-(n-hexylthio))methylene ketal
  参考文献：
  名称：

  Thiol esters from steroid 17.beta.-carboxylic acids: carboxylate activation and internal participation by 17.alpha.-acylates

  摘要：

  DOI：

  10.1021/jo00362a028
• 作为产物：
  描述：

  倍他米松 在 TEA 、 过碘酸 、 二异丙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 17.5h， 生成 17α-acetoxy-9α-fluoro-11β-hydroxy-16β-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid
  参考文献：
  名称：

  Thiol esters from steroid 17.beta.-carboxylic acids: carboxylate activation and internal participation by 17.alpha.-acylates

  摘要：

  DOI：

  10.1021/jo00362a028

文献信息

• Synthesis and Structure-Activity Relationships in a Series of Antiinflammatory Corticosteroid Analogs, Halomethyl Androstane-17.beta.-carbothioates and -17.beta.-carboselenoates
  作者：Gordon H. Phillipps、Esme J. Bailey、Brian M. Bain、Raymond A. Borella、Jacky B. Buckton、John C. Clark、Alice E. Doherty、Alan F. English、Harold Fazakerley

  DOI：10.1021/jm00048a008

  日期：1994.10

  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.
• US4263289A
  申请人：——

  公开号：US4263289A

  公开（公告）日：1981-04-21
• US4310466A
  申请人：——

  公开号：US4310466A

  公开（公告）日：1982-01-12
• US5646136A
  申请人：——

  公开号：US5646136A

  公开（公告）日：1997-07-08