L-倍他米松磷酸钠杂质F | 37926-75-3

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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: L-倍他米松磷酸钠杂质F
• 中文别名: 倍他米松杂质13；倍他米松杂质3(倍他米松17-羧酸)；倍他米松磷酸钠杂质F；(8S,9R,10S,11S,13S,14S,16S,17R)-9-氟-11,17-二羟基-10,13,16-三甲基-3-氧亚基-6,7,8,9,10,11,12,13,14,15,16,17-十二氢-3H-环戊二烯并[A]菲-17-羧酸
• 英文名称: 9α-fluoro-11β,17α-dihydroxy-16β-methyl-3-oxo-androsta-1,4-diene-17β-carboxylic acid
• 英文别名: (8S,10S,11S,13S,14S,16S)-9-Fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta(a)phenanthrene-17-carboxylic acid；(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-carboxylic acid
• CAS: 37926-75-3
• 化学式: C₂₁H₂₇FO₅
• 分子量: 378.441
• InChiKey: PFAGPIFFRLDBRN-IFUSVGBSSA-N

物化性质

• 沸点：
  566.9±50.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于丙酮（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 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：
  94.8
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  L-倍他米松磷酸钠杂质F 在 硫化氢 、 silver fluoride 、 碳酸氢钠 、 二乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 21.75h， 生成 S-fluoromethyl 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：

  倍他米松 以 四氢呋喃 、 水 为溶剂， 生成 L-倍他米松磷酸钠杂质F
  参考文献：
  名称：

  Novel androstane-17.beta.-carboxylic acid esters

  摘要：

  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。

  公开号：

  US04804656A1

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。
• Androstane carbothioic acids
  申请人：Glaxo Group Limited

  公开号：US04578221A1

  公开（公告）日：1986-03-25

  Androstane carbothioic acids of the formula: ##STR1## wherein R.sup.1 represents a hydrogen atom, a hydroxy group in the .alpha.-configuration, a methyl group which may be in either the .alpha.- or .beta.-configuration, or a methylene group; R.sup.2 represents a hydroxy or protected hydroxy group in either the .alpha.- or .beta.-configuration or an oxo group; R.sup.3 represents a hydrogen, bromine, chlorine or fluorine atom; or R.sup.2 and R.sup.3 together represent a carbon-carbon bond or an epoxy group in the .beta.-configuration; R.sup.4 represents a hydrogen or fluorine atom; and the symbol represents a single or double bond and the salts thereof are useful as intermediates in the preparation of anti-inflammatory androstane 17.beta.-carbothioate esters. The compounds of formula I are prepared by reaction of a reactive derivative of a 17.beta.-carboxylic acid corresponding to the compound of formula I with hydrogen sulphide or a sulphide or hydrosulphide salt.

  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。
• Mechanism of base-catalyzed autooxidation of corticosteroids containing 20-keto-21-hydroxyl side chain
  作者：Min Li、Bin Chen、Stephanie Monteiro、Abu M. Rustum

  DOI：10.1016/j.tetlet.2009.05.074

  日期：2009.8

  Corticosteroids and related compounds containing the 20-keto-21-hydroxyl side chain such as betamethasone, betamethasone 9,11-epoxide, dexamethasone, and dexamethasone 9,11-epoxide have been found to undergo facile autooxidation on the 1,3-dihydroxyacetone side chain of their D-rings under strong alkaline conditions to yield five main degradants (17-formyloxy-17-acid, 17-acid, 21-aldehyde, 20-hydroxy-21-acid

  已发现皮质类固醇和含有20-酮-21-羟基侧链的相关化合物，如倍他米松，倍他米松9,11-环氧化物，地塞米松和地塞米松9,11-环氧化物在1,3-二羟基丙酮侧容易发生自氧化在强碱性条件下将它们的D环链合成五种主要降解物（17-甲酰氧-17-酸，17-酸，21-醛，20-羟基-21-酸和17-酮）。自氧化速率与反应中所用碱的强度和浓度相关。提出了一种新的观察到的自氧化机制，其中关键的一步是推定的烯醇化物（由21位碳负离子产生）的容易氧化。拟议的自氧化机制，得到了使用18种LC-MS同位素实验的支持O 2作为氧化剂，可以令人满意地解释观察到的含有20-酮-21-羟基侧链的皮质类固醇的氧化降解模式。
• Specific glucocorticosteriod compound having anti-inflamatory activity
  申请人：Biggadike Keith

  公开号：US20060247219A1

  公开（公告）日：2006-11-02

  A compound of formula (I): (I) wherein X represents O or S; R1 represents C1-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkylmethyl or C3-8 cycloalkenyl any of which optionally may be substituted by one or more methyl groups or halogen atoms or R1 represents aryl, substituted aryl, heteroaryl or substituted heteroaryl; R2 represents hydrogen, methyl, which may be in either the α or β configuration, or methylene; R3 and R4 are the same or different and each independently represents hydrogen, halogen or a methyl group; and represents a single or a double bond; or a physiologically acceptable salt or solvate thereof.

  化合物的式子为（I）：（I）其中X代表O或S；R1代表C1-6烷基，C3-8环烷基，C3-8环烷基甲基或C3-8环烯基，其中任何一个都可以选择性地被一个或多个甲基基团或卤素原子取代，或者R1代表芳基，取代芳基，杂环芳基或取代杂环芳基；R2代表氢，甲基，可以是α或β构型中的任意一种，或亚甲基；R3和R4相同或不同，每个独立地代表氢，卤素或一个甲基基团；代表单键或双键；或其生理上可接受的盐或溶剂化物。
• SPECIFIC GLUCOCORTICOSTEROID COMPOUND HAVING ANTI-INFLAMMATORY ACTIVITY
  申请人：BIGGADIKE KEITH

  公开号：US20080070880A1

  公开（公告）日：2008-03-20

  A compound of formula (I): wherein X represents O or S; R 1 represents C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkylmethyl or C 3-8 cycloalkenyl any of which optionally may be substituted by one or more methyl groups or halogen atoms or R 1 represents aryl, substituted aryl, heteroaryl or substituted heteroaryl; R 2 represents hydrogen, methyl, which may be in either the α or β configuration, or methylene; R 3 and R 4 are the same or different and each independently represents hydrogen, halogen or a methyl group; and represents a single or a double bond; or a physiologically acceptable salt or solvate thereof, and pharmaceutical formulations and methods of use thereof.

  化合物的化学式为(I)，其中X代表O或S；R1代表C1-6烷基，C3-8环烷基，C3-8环烷基甲基或C3-8环烯基，其中任意一个可以选择性地被一个或多个甲基基团或卤素原子取代，或者R1代表芳基，取代芳基，杂环芳基或取代杂环芳基；R2代表氢，甲基（可以是α或β构型）或亚甲基；R3和R4相同或不同，每个独立地代表氢，卤素或一个甲基基团；并表示单键或双键；或其生理上可接受的盐或溶剂化合物，以及其制剂和使用方法。