S-chloromethyl 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carbothioate | 80473-97-8

• 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: S-chloromethyl 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carbothioate
• 英文别名: S-Chloromethyl 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate；[(8S,9R,10S,11S,13S,14S,16S,17R)-17-(chloromethylsulfanylcarbonyl)-9-fluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] propanoate
• CAS: 80473-97-8
• 化学式: C₂₅H₃₂ClFO₅S
• 分子量: 499.043
• InChiKey: REAOHHWVBWYRQC-XGQKBEPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  6
• 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

• 作为反应物：
  描述：

  S-chloromethyl 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carbothioate 在 tris(triphenylphosphine)rhodium (I) chloride 作用下， 以 4,4,4-三氯丁烷-2-酮 、 丙酮 、 苯 为溶剂， 生成 S-Chloromethyl 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-propionyloxyandrost-4-ene-17β-carbothioate
  参考文献：
  名称：

  Androstane carbothioates

  摘要：

  化合物的化学式为##STR1##其中，R1代表氟甲基，氯甲基或溴甲基或2'-氟乙基基团，R2代表羰基R6，其中R6是C1-3烷基或OR2，R3代表氢原子，甲基基团（可以是α或β构型）或亚甲基基团；R4代表氢，氯或氟原子；R5代表氢或氟原子，符号代表单键或双键，这些化合物在局部应用时具有良好的抗炎活性。通过酯化，卤代，还原，去保护和在9,11-双键处反应形成9α-卤代-11β-羟基基团来制备化学式I的化合物。描述和声明了含有化学式I的药物组合物及使用化合物的方法。

  公开号：

  US04335121A1
• 作为产物：
  描述：

  S-chloromethyl 9α-chloro-11β-hydroxy-16β-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate 在 碳酸氢钠 作用下， 生成 S-chloromethyl 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carbothioate
  参考文献：
  名称：

  Androstane carbothioates

  摘要：

  化合物的化学式为##STR1##其中，R1代表氟甲基，氯甲基或溴甲基或2'-氟乙基基团，R2代表羰基R6，其中R6是C1-3烷基或OR2，R3代表氢原子，甲基基团（可以是α或β构型）或亚甲基基团；R4代表氢，氯或氟原子；R5代表氢或氟原子，符号代表单键或双键，这些化合物在局部应用时具有良好的抗炎活性。通过酯化，卤代，还原，去保护和在9,11-双键处反应形成9α-卤代-11β-羟基基团来制备化学式I的化合物。描述和声明了含有化学式I的药物组合物及使用化合物的方法。

  公开号：

  US04335121A1

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.
• PHILLIPPS, G. H.;BAIN, B. MACD.;WILLIAMSON, C.;STEEPLES, I. P.;LAING, S. +
  作者：PHILLIPPS, G. H.、BAIN, B. MACD.、WILLIAMSON, C.、STEEPLES, I. P.、LAING, S. +

  DOI：——

  日期：——
• US4335121A
  申请人：——

  公开号：US4335121A

  公开（公告）日：1982-06-15