9α-chloro-11β,17α-dihydroxy-6α-fluoro-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid | 382631-11-0

• 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
• 英文名称: 9α-chloro-11β,17α-dihydroxy-6α-fluoro-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid
• 英文别名: 9α-chloro-6α-fluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid；(6S,8S,9R,10S,11S,13S,14S,16R,17R)-9-chloro-6-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: 382631-11-0
• 化学式: C₂₁H₂₆ClFO₅
• 分子量: 412.886
• InChiKey: VDIOYBBQXZKXQW-IDIDPBNYSA-N

物化性质

• 沸点：
  601.3±55.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 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：

  9α-chloro-11β,17α-dihydroxy-6α-fluoro-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid 在 N,N'-羰基二咪唑 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.17h， 生成 Furan-2-carboxylic acid (6S,8S,9R,10S,11S,13S,14S,16R,17R)-9-chloro-6-fluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-thiocarboxy-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl ester
  参考文献：
  名称：

  Synthesis and biological properties of novel glucocorticoid androstene C-17 furoate esters

  摘要：

  A series of novel corticosteroid derivatives featuring C-17 furoate ester functionality have been synthesised. Profiling in vitro and in vivo has resulted in the identification of a compound with a longer duration of action and a lower oral side effect profile in rodents compared to budesonide. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.027
• 作为产物：
  描述：

  9-chloro-6α-fluoro-11,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione 在 高碘酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 生成 9α-chloro-11β,17α-dihydroxy-6α-fluoro-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid
  参考文献：
  名称：

  大环内酯类：一类新型的抗炎化合物

  摘要：

  通过将有效的糖皮质激素类固醇与大环内酯类化合物结合在一起，引入了安全糖皮质激素治疗设计的新概念。这些化合物是由9-deokso-9a-aza-9a-同反霉素A和3-descladinosyl-9-deokso-9a-aza-9a-的各种类固醇17β-羧酸和9a- N-（3-氨基烷基）衍生物合成的使用稳定的烷基链的同型阿霉素。结合大环内酯类化合物优先在免疫细胞（特别是吞噬细胞）中积累的特性与经典类固醇的抗炎活性，我们设计了在卵白蛋白（OVA）诱导的哮喘大鼠中表现出良好抗炎活性的分子。描述了这种新型化合物的合成，体外和体内抗炎活性。

  DOI：

  10.1016/j.bmc.2012.10.036

文献信息

• Compounds, compositions and methods for treatment of inflammatory diseases and conditions
  申请人：PLIVA Pharmaceutical Industry, Incorporated

  公开号：US20040014685A1

  公开（公告）日：2004-01-22

  The present invention relates (a) to new compounds represented by Formula I: 1 wherein M represents a macrolide subunit (macrolide moiety) derived from macrolide possessing the property of accumulation in inflammatory cells, S represents a steroid subunit (steroid moiety) derived from steroid drug with anti-inflammatory activity and L represents a linker molecule linking M and S, (b) to their pharmacologically acceptable salts, prodrugs and solvates, (c) to processes and intermediates for their preparation, and (d) to their use in the treatment of inflammatory diseases and conditions in humans and animals. Such compounds inhibit many cytokines and immune mediators involved in immune responses which cause inflammation, allergy, or alloimmunity, including without limitation IL-1, 2, 4, 5, 6, 10, 12, GMCSF, ICAM, and TNF-&agr; Importantly, anti-inflammatory steroids exert a direct anti-inflammatory effect through binding to the glucocorticosteroid receptor.

  本发明涉及以下内容：(a) 由以下式I所表示的新化合物：其中M代表来源于具有在炎症细胞中积聚特性的大环内酯亚基（大环内酯基团），S代表来源于具有抗炎活性的类固醇药物的类固醇亚基（类固醇基团），L代表连接M和S的连接分子，(b) 它们的药理学可接受的盐、前药和溶剂化物，(c) 用于它们的制备的过程和中间体，以及(d) 用于治疗人类和动物的炎症性疾病和症状。这些化合物抑制许多参与导致炎症、过敏或移植免疫反应的细胞因子和免疫介质，包括但不限于IL-1、2、4、5、6、10、12、GMCSF、ICAM和TNF-α。重要的是，抗炎类固醇通过结合糖皮质类固醇受体直接发挥抗炎作用。
• Conjugates of immune cell specific macrolide compounds with anti-inflammatory compounds for improved cellular targeting of anti-inflammatory therapy
  申请人：——

  公开号：US20040198677A1

  公开（公告）日：2004-10-07

  The present invention relates to novel compounds represented by the structure I and pharmaceutical preparations thereof for the treatment of inflammatory diseases in humans and animals.

  本发明涉及一种由结构式I表示的新化合物及其制备的药物制剂，用于治疗人和动物的炎症性疾病。
• Conjugates of Immune Cell Specific Macrolide Compounds with Anti-Inflammatory Compounds for Improved Cellular Targeting of Anti-Inflammatory Therapy
  申请人：MERCEP Mladen

  公开号：US20090105163A1

  公开（公告）日：2009-04-23

  The present invention relates to novel compounds represented by the structure I and pharmaceutical preparations thereof for the treatment of inflammatory diseases in humans and animals.

  本发明涉及一类由结构式I表示的新化合物及其制药制剂，用于治疗人和动物的炎症性疾病。
• Thio etianic acid derivatives, their preparation and pharmaceutical use
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0004741A2

  公开（公告）日：1979-10-17

  Thio etianic acid derivatives of the formula wherein X' is hydrogen, fluoro, or chloro; X2 is hydrogen, fluoro, chloro or bromo; X3 is =C=O Cl may also be =C when X2 is chloro; H R is alkyl of 1 to 6 carbon atoms, or phenyl or benzyl optionally substituted with a substituent on the phenyl ring which is alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon _ atoms or halo; R1 is hydrogen or alkanoyl of 2 to 6 carbon atoms when R2 is hydrogen, a-methyl or β-methyl or OR1 and R2 together are 16a, 17a-isopropylidenedioxy; and the solid and broken lines between C-1 and C-2 represent a double or single bond; are useful an anti-inflammatory steroids. They can be prepared by reacting the corresponding 17β-carboxylic acid or a reactive derivative thereof with an alkali metal salt of RSH.

  式中的硫代乙酸衍生物 式中 X'是氢、氟或氯 X2 是氢、氟、氯或溴 X3 是 =C=O Cl 当 X2 为氯时，也可以是 =C；H R 是 1 至 6 个碳原子的烷基，或苯基或苄基，可选择被苯基环上的 1 至 4 个碳原子的烷基、1 至 4 个碳 _ 原子的烷氧基或卤素取代； 当 R2 为氢、a-甲基或 β-甲基时，R1 为氢或 2 至 6 个碳原子的烷酰基，或 OR1 和 R2 一起为 16a、17a-异亚丙基二氧基；C-1 和 C-2 之间的实线和断线代表双键或单键。它们可以通过相应的 17β 羧酸或其活性衍生物与 RSH 的碱金属盐反应来制备。
• ANDROSTENE DERIVATIVES
  申请人：Soft Drugs, Inc.

  公开号：EP0902789B1

  公开（公告）日：2002-01-23