9α-fluoro-11β,17α-dihydroxy-16β-methyl-3-oxoandrosta-1,4-diene-17β-carbothioic acid | 80473-85-4

• 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-16β-methyl-3-oxoandrosta-1,4-diene-17β-carbothioic acid
• 英文别名: (8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carbothioic S-acid
• CAS: 80473-85-4
• 化学式: C₂₁H₂₇FO₄S
• 分子量: 394.507
• InChiKey: IKUUMGMKUCTRGD-IFUSVGBSSA-N

物化性质

• 沸点：
  548.3±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：
  27
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 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-16β-methyl-3-oxoandrosta-1,4-diene-17β-carbothioic acid 在 碳酸氢钠 、 二乙胺 、 sodium iodide 、 lithium bromide 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 丙酮 为溶剂， 反应 123.75h， 生成 S-bromomethyl 9α-fluoro-11β-hydroxy-16β-methyl-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：

  L-倍他米松磷酸钠杂质F 在 N,N'-羰基二咪唑 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 9α-fluoro-11β,17α-dihydroxy-16β-methyl-3-oxoandrosta-1,4-diene-17β-carbothioic acid
  参考文献：
  名称：

  Androstane carbothioic acids

  摘要：

  公式为：##STR1## 其中，R.sup.1代表氢原子，α-构型的羟基，可能处于α-或β-构型的甲基或亚甲基基团；R.sup.2代表α-或β-构型的羟基或保护羟基，或氧代基；R.sup.3代表氢、溴、氯或氟原子；或者R.sup.2和R.sup.3一起代表β-构型的碳-碳键或环氧基；R.sup.4代表氢或氟原子；符号代表单键或双键。该化合物的盐在制备抗炎症的17β-羧硫酸酯雄烷中间体时有用。公式I的化合物是通过17β-羧酸的反应衍生物与硫化氢或硫化物或氢硫化物盐反应制备的。

  公开号：

  US04578221A1

文献信息

• [EN] GLUCOCORTICOID RECEPTOR AGONIST AND IMMUNOCONJUGATES THEREOF<br/>[FR] AGONISTE DU RÉCEPTEUR DES GLUCOCORTICOÏDES ET IMMUNOCONJUGUÉS DE CELUI-CI
  申请人：ABBVIE INC

  公开号：WO2021161263A1

  公开（公告）日：2021-08-19

  Provided herein are glucocorticoid receptor agonist immunoconjugates, glucocorticoid receptor agonists, pharmaceutical compositiosn including the same, and methods of using the same.

  本文提供了糖皮质激素受体激动剂免疫结合物、糖皮质激素受体激动剂、包括相同成分的药物组合物，以及使用它们的方法。
• Novel Anti-Inflammatory Androstane Derivatives
  申请人：Biggadike Keith

  公开号：US20080317833A1

  公开（公告）日：2008-12-25

  There are provided according to the invention pharmaceutical compositions comprising a compound of formula (I) wherein R 1 represents C 1-6 alkyl or C 1-6 haloalkyl; R 2 represents —C(═O)-aryl or —C(═O)-heteroaryl, wherein said heteroaryl is a 5 member heterocyclic aromatic ring containing 1-3 hetero atoms selected from N and S, or a 5 member heterocyclic aromatic ring containing 2-3 hetero atoms selected from N, O and S, or a 6 member heterocyclic aromatic ring containing 1-3 hetero atoms selected from N, O and S; R 3 represents hydrogen, methyl (which may be in either the α or β configuration) or methylene; R 4 and R 5 are the same or different and each represents hydrogen or halogen; and represents a single or a double bond; or a physiologically acceptably salt or solvate thereof; and another therapeutically active agent; in admixture with one or more physiologically acceptable diluents or carriers.

  本发明提供了制剂，其中包括化合物(I)，其式中R1代表C1-6烷基或C1-6卤代烷基；R2代表—C(═O)-芳基或—C(═O)-杂芳基，其中所述的杂芳基是一个含有1-3个异原子（选自N和S）的5元杂环芳基环，或者是一个含有2-3个异原子（选自N、O和S）的5元杂环芳基环，或者是一个含有1-3个异原子（选自N、O和S）的6元杂环芳基环；R3代表氢、甲基（可以是α或β构型）或亚甲基；R4和R5相同或不同，且每个代表氢或卤素；并且代表单键或双键；或其生理上可接受的盐或溶剂；以及另一种治疗活性剂；与一种或多种生理上可接受的稀释剂或载体混合。
• NOVEL ANTI-INFLAMMATORY ANDROSTANE DERIVATIVES
  申请人：——

  公开号：US20030045512A1

  公开（公告）日：2003-03-06

  According to one aspect of the invention, there is provided a pharmaceutical formulation for administration by inhalation comprising a compound of formula (I), 1 wherein R 1 represents C 1-6 alkyl or C 1-6 haloalkyl; R 2 represents —C(═O)-aryl or —C(═O)-heteroaryl; R 3 represents hydrogen, methyl (which may be in either the &agr; or &bgr; configuration) or methylene; R 4 and R 5 are the same or different and each represents hydrogen or halogen; and represents a single or a double bond; and salts and solvates thereof together with a long-acting &bgr; 2 -adrenoreceptor agonist which formulation has a therapeutically useful effect in the treatment of inflammatory disorders of the respiratory tract over a period of 24 hours or more.

  根据本发明的一个方面，提供了一种用于吸入给药的药物配方，其包括式（I）的化合物，其中R1表示C1-6烷基或C1-6卤代烷基；R2表示—C（═O）-芳基或—C（═O）-杂环芳基；R3表示氢、甲基（可以处于α或β构型中）或亚甲基；R4和R5相同或不同，每个表示氢或卤素；表示单键或双键；以及其盐和溶剂合物，连同一种长效的β2-肾上腺素受体激动剂，该配方在治疗呼吸道炎症性疾病方面具有治疗上有用的效果，持续24小时或更长时间。
• Novel anti-inflammatory androstane derivatives
  申请人：Biggadike Keith

  公开号：US20050054622A1

  公开（公告）日：2005-03-10

  There are provided compounds of formula (I) wherein R 1 represents O, S or NH; R 2 represents —C(═O)-aryl or —C(═O)-heteroaryl; R 3 represents hydrogen, methyl (which may be in either the α or β configuration) or methylene; R 4 and R 5 are the same or different and each represents hydrogen or halogen; and represents a single or a double bond; and salts and solvates thereof; process for preparing them, compositions containing them and their use in therapy.

  提供了化合物的公式（I），其中R1代表O，S或NH; R2代表—C（═O）-芳基或—C（═O）-杂环基; R3代表氢，甲基（可以是α或β构型）或亚甲基; R4和R5相同或不同，每个代表氢或卤素; 代表单键或双键; 以及其盐和溶剂化物; 制备它们的过程，含有它们的组合物以及它们在治疗中的用途。
• Formulation for inhalation comprising a glucocorticoid and a beta 2-adrenoreceptor agonist
  申请人：GLAXO GROUP LIMITED

  公开号：EP1757281A2

  公开（公告）日：2007-02-28

  According to one aspect of the invention, there is provided a pharmaceutical formulation for administration by inhalation comprising a compound of formula (I), wherein R1 represents C1-6 alkyl or C1-6 haloalkyl; R2 represents -C(=O)-aryl or -C(=O)-heteroaryl; R3 represents hydrogen, methyl (which may be in either the α or β configuration) or methylene; R4 and R5 are the same or different and each represents hydrogen or halogen; and represents a single or a double bond; and salts and solvates thereof together with a long-acting β2-adrenoreceptor agonist which formulation has a therapeutically useful effect in the treatment of inflammatory disorders of the respiratory tract over a period of 24 hours or more.

  根据本发明的一个方面，提供了一种用于吸入给药的药物制剂，其中包含式 (I) 化合物、 其中 R1 代表 C1-6 烷基或 C1-6 卤代烷基； R2 代表-C(＝O)-芳基或-C(＝O)-杂芳基； R3 代表氢、甲基（可以是 α 或 β 构型）或亚甲基； R4 和 R5 相同或不同，各自代表氢或卤素；以及 代表单键或双键； 及其盐类和溶剂，以及长效 β2-肾上腺素受体激动剂，该制剂在治疗呼吸道炎症性疾病方面具有 24 小时或更长时间的治疗作用。