9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carboxylic acid | 37927-23-4

• 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-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carboxylic acid
• 英文别名: 9α-fluoro-11β-hydroxy-17α-(propionyloxy)-16β-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid；(8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-propanoyloxy-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carboxylic acid
• CAS: 37927-23-4
• 化学式: C₂₄H₃₁FO₆
• 分子量: 434.505
• InChiKey: AMFRKDPPWBPDOJ-INZHXJBESA-N

物化性质

• 沸点：
  576.0±50.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 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：

  9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-1,4-diene-17β-carboxylic acid 在 硫化氢 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioic acid
  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 三乙胺 、 二异丙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 9α-fluoro-11β-hydroxy-16β-methyl-3-oxo-17α-(propionyloxy)androsta-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

• Novel androstane-17.beta.-carboxylic acid esters
  申请人：Aktiebolaget Draco

  公开号：US04804656A1

  公开（公告）日：1989-02-14

  The invention refers to compounds having anti-inflammatory activity characterized by the formula ##STR1## or a stereoisomeric component thereof, in which formula X.sub.1 represents a hydrogen, chlorine, bromine or fluorine atom; X.sub.2 represents a hydrogen, chlorine, bromine or fluorine atom; R.sub.1 represents a .beta.-hydroxy group, a .beta.-chlorine atom or an oxo group; R.sub.2 represents a hydrogen atom, a methylene group or an .alpha.- or .beta.-methyl group; R.sub.3 represents a hydrogen atom or an acyl group of 1 through 8 carbon atoms; R.sub.4 represents a hydrogen atom, a (C.sub.1 -C.sub.5) alkyl group or a phenyl group; R.sub.5 represents a hydrogen atom, a (C.sub.1 -C.sub.5) alkyl group or a phenyl group; Y represents either CR.sub.7 R.sub.8, O, S or NR.sub.9, where R.sub.7, R.sub.8 and R.sub.9 are selected from hydrogen or from straight or branched hydrocarbon chains having 1-8 carbon atoms or from a phenyl group. R.sub.6 represents a hydrogen; a methyl group; a phenyl or an alkenyl or cycloalkylene group optionally substituted by alkyl, nitro, carboxy, alkoxy, halogen, cyano, carbalkoxy and trifluoromethyl group(s); a (C.sub.1 -C.sub.5) alkyl group substituted by at least one halogen atom; a saturated or unsaturated carbocyclic or heterocyclic (O, S, N) ring system containing 3-10 atoms in the ring system; a C.sub.1 alkyl group substituted by either one or two alicyclic or aromatic 3,4,5 or 6-numbered ring system(s) or one, two or three straight or branched alkyl or alkenyl group(s) of 1 through 18 carbon atoms; and represents a single or double bond. The invention also refers to a process and intermediates for the preparation of these compounds, a pharmaceutical preparation containing one of the compounds and a method for the treatment of inflammatory conditions.

  该发明涉及具有抗炎活性的化合物，其特征化学式为##STR1##或其立体异构体，其中化学式中X.sub.1代表氢、氯、溴或氟原子；X.sub.2代表氢、氯、溴或氟原子；R.sub.1代表β-羟基、β-氯原子或羰基；R.sub.2代表氢原子、亚甲基基团或α-或β-甲基基团；R.sub.3代表氢原子或1至8个碳原子的酰基基团；R.sub.4代表氢原子、(C.sub.1 -C.sub.5)烷基基团或苯基；R.sub.5代表氢原子、(C.sub.1 -C.sub.5)烷基基团或苯基；Y代表CR.sub.7 R.sub.8、O、S或NR.sub.9，其中R.sub.7、R.sub.8和R.sub.9选自氢或由1-8个碳原子的直链或支链烃基链或苯基。R.sub.6代表氢原子；甲基基团；苯基或烯基或环烷基基团，可选择地被烷基、硝基、羧基、烷氧基、卤素、氰基、羰基烷氧基和三氟甲基基团取代；由至少一个卤素原子取代的(C.sub.1 -C.sub.5)烷基基团；含有3-10个原子的饱和或不饱和碳环或杂环(O、S、N)环系统；由一个或两个脂环或芳香3,4,5或6号环系统取代的C.sub.1烷基基团；以及表示单键或双键。该发明还涉及制备这些化合物的过程和中间体，含有其中一种化合物的药物制剂以及用于治疗炎症症状的方法。
• Androstane-17beta-carboxylic acids and processes for the preparation thereof
  申请人：GLAXO LABORATORIES LIMITED

  公开号：US03828080A1

  公开（公告）日：1974-08-06
• Androstane-17-beta-carboxylic-acid esters, process for their preparation and pharmaceutical compound containing them
  申请人：Aktiebolaget Draco

  公开号：EP0200692B1

  公开（公告）日：1991-09-11
• EDWARDS, J. A.
  作者：EDWARDS, J. A.

  DOI：——

  日期：——
• PHILLIPPS, G. H.;BAIN, B. M. D.;WILLIAMSON, CH.;STEEPLES, J. PH.;SAING, S+
  作者：PHILLIPPS, G. H.、BAIN, B. M. D.、WILLIAMSON, CH.、STEEPLES, J. PH.、SAING, S+

  DOI：——

  日期：——