(6alpha,11beta,16alpha,17alpha)-6,9-二氟-11-羟基-16,17-[(1-甲基乙亚基)二(氧基)]-3-氧代雄甾-1,4-二烯-17-羧酸 | 65751-34-0

• 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
• 中文名称: (6alpha,11beta,16alpha,17alpha)-6,9-二氟-11-羟基-16,17-[(1-甲基乙亚基)二(氧基)]-3-氧代雄甾-1,4-二烯-17-羧酸
• 英文名称: 11β-hydroxy-16α,17α-isopropylidenedioxy-3-oxo-6α,9α-difluoroandrosta-1,4-diene-17β-carboxylic acid
• 英文别名: 6α,9α-difluoro-11β,16α,17α-trihydroxy-3-oxoandrosta-1,4-diene-17β-carboxylic acid 16,17-acetonide；(2S,6aS,6bR,7S,8aS,8bS,11aR,12aS,12bS)-2,6b-difluoro-7-hydroxy-6a,8a,10,10-tetramethyl-4-oxo-1,2,4,6a,6b,7,8,8a,11a,12,12a,12b-dodecahydro-8bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxole-8b-carboxylic acid；6α,9α-difluoro-11β-hydroxy-16α,17α-[(1-methylethylidene)-bis(oxy)]androsta-1,4-diene-3-one-17β-carboxylic acid；6α,9α-difluoro-11β,16α,17α-trihydroxy-3-oxoandrosta-1,4-diene-17β-carboxylic 16,17-acetonide acid；(4aS,4bR,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-4a,6a,8,8-tetramethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]-indeno[1,2-d][1,3]dioxole-6b-carboxylic acid；6α,9α-difluoro-11β-hydroxy-16α,17α-isopropylidenedioxy-3-oxoandrosta-1,4-diene 17β-carboxylic acid；6alpha,9-Difluoro-11beta-hydroxy-16alpha,17-(1-methylethylidenedioxy)-3-oxoandrosta-1,4-diene-17beta-carboxylic acid；(1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-6,6,9,13-tetramethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-diene-8-carboxylic acid
• CAS: 65751-34-0
• 化学式: C₂₃H₂₈F₂O₆
• 分子量: 438.469
• InChiKey: NURGGCFNQHBYEW-QXWOZTMISA-N

物化性质

• 沸点：
  576.0±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  31
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (6alpha,11beta,16alpha,17alpha)-6,9-二氟-11-羟基-16,17-[(1-甲基乙亚基)二(氧基)]-3-氧代雄甾-1,4-二烯-17-羧酸 在 高氯酸 甲酸 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 6.0h， 生成 S-{[(4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-4a,6a-dimethyl-2-oxo-8-(2-thienyl)-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6b-yl]carbonyl} dimethylthiocarbamate
  参考文献：
  名称：

  [EN] 16 ALPHA, 17 ALPHA-ACETAL GLUCOCORTICOSTEROIDAL DERIVATIVES AND THEIR USE
  [FR] DÉRIVÉS DE GLUCOCORTICOSTÉROÏDES DE 16 ALPHA, 17 ALPHA-ACÉTAL ET LEUR UTILISATION

  摘要：

  公开号：

  WO2009108118A9
• 作为产物：
  描述：

  醋酸氟轻松 在 air 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以75%的产率得到(6alpha,11beta,16alpha,17alpha)-6,9-二氟-11-羟基-16,17-[(1-甲基乙亚基)二(氧基)]-3-氧代雄甾-1,4-二烯-17-羧酸
  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

• [EN] 17.BETA- (ALPHA-HYDROXY) -ESTERS OF ANDROSTANES AS INTERMEDIATES FOR THE PREPARATION FOR THE PREPARATION OF 17.BETA.-FLUORINATED-ANDROSTANE ESTERS<br/>[FR] ESTERS DE 17-BETA-(ALPHA-HYDROXY) D'ANTROSTANES, UTILISES COMME INTERMEDIAIRES DANS LA PREPARATION D'ESTERS D'ANDROSTANE 15-BETA FLUORES.
  申请人：FARMABIOS SRL

  公开号：WO2004052912A1

  公开（公告）日：2004-06-24

  Process for the preparation of polyhalogenated steroids, in particular of androstanic fluoro derivatives corticosteroids by means of the formation of new androstanic S-hydroxy alkyl or aralkyl-17-carbothioate intermediates.

  通过形成新的雄甾烷S-羟基烷基或芳基-17-羰硫酸酯中间体，制备多卤代类固醇，特别是雄甾烷氟衍生物皮质类固醇的方法。
• Anti-inflammatory 17β-Thioalkyl-16α,17α-ketal and -acetal Androstanes:  A New Class of Airway Selective Steroids for the Treatment of Asthma
  作者：Michael J. Ashton、Christopher Lawrence、Jan-Anders Karlsson、Keith A. J. Stuttle、Christopher G. Newton、Bernard Y. J. Vacher、Stephen Webber、Michael J. Withnall

  DOI：10.1021/jm9604639

  日期：1996.1.1

  of a new class of 17beta-thioalkyl-16alpha,17alpha-ketal and -acetal androstanes are described. This new class of steroids was made by fragmentation of 2-thioxo-1,2-dihydropyrid-1-yl esters of the corresponding 17-acids to the 17-radical. The radical generated was trapped using a variety of radicophilic disulfides, giving a steroidal D-ring having acetal or ketal functionality at C-16 and C-17, together

  描述了新型的17β-硫代烷基-16α，17α-缩酮和-缩醛雄烷烃的合成和抗炎作用。这类新的类固醇是通过将相应的17个酸的2-硫代-1,2-二氢吡啶-1-基酯片段化为17-自由基制成的。使用多种亲二硫键捕获生成的自由基，得到在C-16和C-17处具有乙缩醛或缩酮功能的甾族D环，以及在C-17处具有硫键。该系列化合物与糖皮质激素受体高效结合，是功能性激动剂，通过在体外诱导大鼠肝细胞系中酪氨酸氨基转移酶活性的能力来衡量。当直接施用于呼吸道时，这些17β-硫代烷基雄烷酮可有效抑制Sephadex诱导的大鼠肺部炎症。与目前可获得的吸入式糖皮质激素相比，高的局部效力以及诱导全身性类糖皮质激素样副作用（大鼠胸腺退化）的低倾向使本发明化合物具有高度的气道选择性。本文所述的17β-硫代烷基-16α，17α-缩酮雄烷酮可用于治疗炎性疾病例如哮喘。
• 17&bgr;-2-oxo-tetrahydrofuranyl)-carbothioic acid ester, -carboxylic acid ester and -carboxylic acid amide androstane derivatives
  申请人：Glaxo Wellcome Inc.

  公开号：US06197761B1

  公开（公告）日：2001-03-06

  Compounds of the androstane series are described having general formula and solvates thereof, in which R1 represents O, S or NH; R2 individually represents OC(═O)C1-6 alkyl; R3 individually represents hydrogen, methyl (which may be in either the &agr; or &bgr; configuration) or methylene; or R2 and R3 together represent where R6 and R7 are the same or different and each represents hydrogen or C1-6 alkyl; R4 and R5 are the same or different and each represents hydrogen or halogen and represents a single or a double bond. These compounds and their solvates have use in medicine as anti-inflammatory or anti-allergic agents.

  本发明涉及一般式及其溶剂化物的雄甾烷系化合物，其中R1代表O、S或NH；R2分别代表OC(═O)C1-6烷基；R3分别代表氢、甲基（可以是α或β构型）或亚甲基；或者R2和R3一起代表其中R6和R7相同或不同，分别代表氢或C1-6烷基；R4和R5相同或不同，分别代表氢或卤素，表示单键或双键。这些化合物及其溶剂化物在医学上可用作抗炎或抗过敏剂。
• Process for the manufacture of steroid carboxylic acids and the esters
  申请人：Ciba-Geigy Corporation

  公开号：US04119625A1

  公开（公告）日：1978-10-10

  The present invention provides a novel process for the manufacture of 17- and 17a-carboxylic acids of the androstane and D-homo-androstane series respectively, of the following partial formula of the ring D ##STR1## wherein R represents a hydrogen atom or an unsubstituted or substituted hydrocarbon radical or a free or functionally modified hydroxyl group, and wherein the carboxyl group can be in the .alpha.- or .beta.-position, and of the salts and functional acid derivatives thereof, in particular their esters. The new process consists in the oxidative degradation of the side chain of corrsponding 20, 21-ketoaldehydes of the pregnane or D-homopregnane series or of the 17.alpha.-pregnane or 17a.alpha.-D-homopregnane series with an organic peracid in an inert solvent, preferably at temperatures between -20 and +30.degree. C, and optionally converting free functional groups present into their derivatives or setting free functional groups from substituents which are derivatives of such groups.

  本发明提供了一种制造17-和17a-环丙烷和D-环丙烷系列的羧酸的新工艺，其部分分子式如下：其中R代表氢原子或未取代或取代的烃基或自由或功能修饰的羟基基团，羧基可以在α或β位置，以及它们的盐和功能酸衍生物，特别是它们的酯。新工艺包括在惰性溶剂中，使用有机过氧酸氧化相应的孕烷或D-孕烷系列的20,21-酮醛侧链，或17α-孕烷或17aα-D-孕烷系列的20,21-酮醛侧链，并在-20至+30℃的温度下进行，可选择将存在的自由功能基团转化为其衍生物，或从衍生物中释放出功能基团的取代基。
• 16,17-acetalsubstituted androstane-17.beta.-carboxylic acid esters
  申请人：Aktiebolaget Draco

  公开号：US04950659A1

  公开（公告）日：1990-08-21

  The invention refers to compounds having anti-inflamatory activity characterized by the formula ##STR1## or a stereoisomeric component thereof, in which formula the 1,2-position is saturated or is a double bond X.sub.1 is selected from hydrogen, fluorine, chlorine and bromine X.sub.2 is selected from hydrogen, fluorine, chlorine and bromine R.sub.1 is selected from hydrogen or a straight or branched hydrocarbon chain having 1-4 carbon atoms R.sub.2 is selected from hydrogen or straight and branched hydrocarbon chains having 1-10 carbon atoms and R.sub.3 is selected from ##STR2## is O or S R.sub.4 is selected from hydrogen, straight or branched hydrocarbon chains having 1-10 carbon atoms or from phenyl R.sub.5 is selected from hydrogen or methyl and R.sub.6 is selected from hydrogen, straight or branched, saturated or unsaturated hydrocarbon chains having 1-10 carbon atoms, an alkyl group substituted by at least one halogen atom, a heterocyclic ring system containing 3-10 atoms in the ring system, ##STR3## (m=0,1,2; n=2,3,4,5,6), phenyl or benzyl groups which are unsubstituted or substituted by one or more alkyl, nitro, carboxy, alkoxy, halogen, cyano, carbalkoxy or trifluoromethyl group(s), provided that when R.sub.2 is hydrogen R.sub.1 is methyl. The invention also refers to a process and intermediates for the prearation of these compunds, a pharmaceutical preparation containing one of the compunds and a method for the treatment of inflammatory conditions.

  本发明涉及具有抗炎活性的化合物，其特征为式##STR1##或其立体异构体组分，其中式中1,2位是饱和的或是双键，X.sub.1选自氢、氟、氯和溴，X.sub.2选自氢、氟、氯和溴，R.sub.1选自氢或具有1-4个碳原子的直链或支链烃基，R.sub.2选自氢或具有1-10个碳原子的直链和支链烃基，R.sub.3选自##STR2##是O或S，R.sub.4选自氢、具有1-10个碳原子的直链或支链烃基或苯基，R.sub.5选自氢或甲基，R.sub.6选自氢、具有1-10个碳原子的直链或支链、饱和或不饱和烃基，被至少一个卤素原子取代的烷基，含有3-10个原子的杂环环系统，##STR3##(m=0,1,2; n=2,3,4,5,6)，苯基或苄基，其未取代或被一个或多个烷基、硝基、羧基、烷氧基、卤素、氰基、羧酸烷酯或三氟甲基基团取代，但当R.sub.2为氢时，R.sub.1为甲基。本发明还涉及用于制备这些化合物的过程和中间体、含有其中一种化合物的制药制剂以及治疗炎症状况的方法。