17β-N,N-dimethylthiocarbamoyloxycarbonyl-6α,9α-difluoro-11β,16α,17α-trihydroxy-3-oxoandrosta-1,4-diene 16,17-acetonide | 709002-86-8

• 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: 17β-N,N-dimethylthiocarbamoyloxycarbonyl-6α,9α-difluoro-11β,16α,17α-trihydroxy-3-oxoandrosta-1,4-diene 16,17-acetonide
• 英文别名: S-{[(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]dioxol-6b-yl]carbonyl}dimethylthiocarbamate；S-(dimethylcarbamoyl) (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-carbothioate
• CAS: 709002-86-8
• 化学式: C₂₆H₃₃F₂NO₆S
• 分子量: 525.614
• InChiKey: LOZLGPKSLYXZGN-NGXOUOCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  36
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  17β-N,N-dimethylthiocarbamoyloxycarbonyl-6α,9α-difluoro-11β,16α,17α-trihydroxy-3-oxoandrosta-1,4-diene 16,17-acetonide 在 甲醇 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 7.0h， 生成 S-(cyanomethyl) (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-carbothioate
  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 高碘酸 、 三乙胺 、 sodium iodide 作用下， 以 1,4-二氧六环 、 水 、 丙酮 为溶剂， 反应 8.5h， 生成 17β-N,N-dimethylthiocarbamoyloxycarbonyl-6α,9α-difluoro-11β,16α,17α-trihydroxy-3-oxoandrosta-1,4-diene 16,17-acetonide
  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

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。
• 16 Alpha, 17 Alpha-Acetal Glucocorticosteroidal Derivatives and their Use
  申请人：Burkamp Frank

  公开号：US20110294766A1

  公开（公告）日：2011-12-01

  The present invention provides compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in the specification, a process for their preparation, pharmaceutical compositions containing them and their use in therapy.

  本发明提供了式（I）的化合物，其中R1、R2、R3、R4、R5和R6如规范中所定义，其制备方法，含有它们的制药组合物以及它们在治疗中的使用。
• 新型糖皮质激素、其制备方法及用途
  申请人：[en]TIANJIN PHARMACEUTICAL BIOTECHNOLOGY CO., LTD.;[zh]津药生物科技（天津）有限公司

  公开号：WO2024125639A1

  公开（公告）日：2024-06-20

  本发明属于药物化学技术领域，具体涉及一种新型糖皮质激素、其制备方法及用途，包括式I化合物、其旋光异构体、其可药用的盐或其溶剂合物，其中式I化合物的结构式如文中所示。本发明提供的化合物具有高的血浆清除速率和短的半衰期，全身药物暴露量低，对糖皮质激素受体(GR)的靶点选择性更高，可显著降低糖皮质激素药物全身吸收带来的副作用。对动物哮喘、葡萄膜炎、干眼症、炎症性肠病及银屑病等，均具有显著的抗炎活性。本发明化合物具有良好的安全性，在豚鼠眼部连续给药未检测到眼压异常，以及在大鼠皮肤连续给药后表皮层厚度未发生明显异常。
• [EN] 16 ALPHA, 17 ALPA-ACETAL GLUCOCORTICOSTEROIDAL DERIVATIVES AND THEIR USE<br/>[FR] DÉRIVÉS DE GLUCOCORTICOSTÉROÏDES DE 16 ALPHA, 17 ALPHA-ACÉTAL ET LEUR UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2009108118A1

  公开（公告）日：2009-09-03

  The present invention provides compounds of formula (I) wherein R1, R2, R3, R4, R5 and R6 are as defined in the specification, a process for their preparation, pharmaceutical compositions containing them and their use in therapy.
• [EN] NOVEL STEROID PAYLOADS, STEROID LINKERS, ADCs CONTAINING AND USE THEREOF<br/>[FR] NOUVELLE CHARGE UTILE DE STÉROÏDE, LIEURS DE STÉROÏDES, CAM LES CONTENANT ET UTILISATION ASSOCIÉE
  申请人：[en]IMMUNEXT, INC.

  公开号：WO2022150637A1

  公开（公告）日：2022-07-14

  The invention provides novel glucocorticosteroids, glucocorticosteroid-linkers and antibody drug conjugates (ADC's) comprising an antibody or antibody fragment which binds to an antigen expressed on immune cells, optionally an antigen expressed on human immune cells. In some instances the ADCs comprise an anti-human VISTA (V-region Immunoglobulin-containing Suppressor of T cell Activation(1)) antibody or anti-VISTA antigen-binding antibody fragment which binds to VISTA expressing cells at physiologic pH having a short serum half-life (≈ 24-72 or 24-48 or 12-24 hours or less in a human VISTA knock-in rodent or ((≈ 1-3.5 days or less in a human or non-human primate). In some instances these ADCs have a rapid onset of action and are potent for prolonged duration as they are very effectively internalized by immune cells in large amounts where they are cleaved releasing large amounts of active steroid payload. The invention also relates to the use of such ADCs and novel steroids for the treatment of autoimmune, allergic and inflammatory conditions. The invention further relates to methods for reducing the adverse side effects and/or enhancing the efficacy of glucocorticoid receptor agonists by using such ADCs to selectively deliver these anti-inflammatory agents to target immune cells, such as monocytes, neutrophils, B cells, T cells, Tregs, eosinophils, NK cells, macrophages, myeloid cells, et al., and particularly myeloid cells, thereby reducing potential toxicity to non-target cells.