9α-fluoro-11β,17α-dihydroxy-3-oxoandrosta-1,4-diene-17β-carbothioic acid | 80473-91-2

• 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,17α-dihydroxy-3-oxoandrosta-1,4-diene-17β-carbothioic acid
• 英文别名: (11β,17α)-9-fluoro-11,17-dihydroxy-3-oxoandrosta-1,4-diene-17-carbothioic S-acid；(8S,9R,10S,11S,13S,14S,17R)-9-fluoro-11,17-dihydroxy-10,13-dimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carbothioic S-acid
• CAS: 80473-91-2
• 化学式: C₂₀H₂₅FO₄S
• 分子量: 380.481
• InChiKey: OVILLYIPGVRALL-VJLCOJPHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  75.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9α-fluoro-11β,17α-dihydroxy-3-oxoandrosta-1,4-diene-17β-carbothioic acid 在 碳酸氢钠 、 二乙胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 丙酮 为溶剂， 反应 3.75h， 生成 S-chloromethyl 9α-fluoro-11β-hydroxy-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：

  9-氟醋酸泼尼松龙 在 水 、 高碘酸 、 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、103.42 kPa 条件下， 反应 6.5h， 生成 9α-fluoro-11β,17α-dihydroxy-3-oxoandrosta-1,4-diene-17β-carbothioic acid
  参考文献：
  名称：

  糖皮质激素受体激动剂及其偶联物

  摘要：

  本申请涉及医药领域，具体涉及一种糖皮质激素受体激动剂的抗体-药物偶联物。具体地，本申请提供了一类糖皮质激素受体激动剂，其具有优良的激动活性。本申请还提供了用于偶联的药物-连接子化合物，所述药物为糖皮质激素受体激动剂。本申请还提供了药物-连接子化合物与抗体偶联所制得的抗体-药物偶联物，其具有良好的药物偶联均一性，对类风湿性关节炎等炎症性疾病具有优异的治疗效果。本申请进一步提供所述糖皮质激素受体激动剂及其抗体-药物偶联物的制备方法及其在医药领域的应用。

  公开号：

  WO2024149093A1

文献信息

• [EN] NOVEL GLUCOCORTICOID RECEPTOR AGONISTS<br/>[FR] NOUVEAUX AGONISTES DU RÉCEPTEUR DES GLUCOCORTICOÏDES
  申请人：PFIZER LTD

  公开号：WO2010136940A1

  公开（公告）日：2010-12-02

  This invention relates to novel glucocorticoid receptor agonists of formula (I) and to processes and intermediates for their preparation. The present invention also relates to pharmaceutical compositions containing these compounds, to their combination with one or more other therapeutic agents, as well as to their use for the treatment of a number of inflammatory and allergic diseases, disorders and conditions.

  本发明涉及一种新型的化学式（I）的糖皮质激素受体激动剂，以及用于它们的制备的过程和中间体。本发明还涉及含有这些化合物的药物组合物，以及它们与一个或多个其他治疗剂的联合使用，以及它们用于治疗多种炎症和过敏性疾病、紊乱和症状。
• Novel Glucocorticoid Receptor Agonists
  申请人：Glossop Paul Alan

  公开号：US20100303758A1

  公开（公告）日：2010-12-02

  This invention relates to novel glucocorticoid receptor agonists of formula (I): and to processes and intermediates for their preparation. The present invention also relates to pharmaceutical compositions containing these compounds, to their combination with one or more other therapeutic agents, as well as to their use for the treatment of a number of inflammatory and allergic diseases, disorders and conditions.

  本发明涉及一种新的糖皮质激素受体激动剂，其化学式为（I）：以及其制备过程和中间体。本发明还涉及含有这些化合物的药物组合物，以及它们与一个或多个其他治疗剂的组合，以及它们用于治疗多种炎症和过敏性疾病，失调和状况。
• US4335121A
  申请人：——

  公开号：US4335121A

  公开（公告）日：1982-06-15
• US4578221A
  申请人：——

  公开号：US4578221A

  公开（公告）日：1986-03-25
• US4650610A
  申请人：——

  公开号：US4650610A

  公开（公告）日：1987-03-17