2-((10S,13S)-10,13-dimethyl-3-oxo-6,7,8,10,12,13,14,15-octahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl acetate | 37413-91-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 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: 2-((10S,13S)-10,13-dimethyl-3-oxo-6,7,8,10,12,13,14,15-octahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl acetate
• 英文别名: [2-[(10S,13S)-10,13-dimethyl-3-oxo-6,7,8,12,14,15-hexahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate
• CAS: 37413-91-5
• 化学式: C₂₃H₂₆O₄
• 分子量: 366.457
• InChiKey: UFEOMHFPJREVTP-RKGHMJSLSA-N

物化性质

• 熔点：
  173-175°C
• 沸点：
  534.6±50.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：100 mg/mL（272.89 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

制备方法与用途

醋酸四烯物（21-羟基孕甾-1,4,9(11),16-四烯-3,20-二酮-21-醋酸酯，3TR）是合成曲安奈德、地塞米松和布地奈德等甾体药物的重要中间体。

生物活性 21-Acetoxypregna-1,4,9(11),16-tetraene-3,20-dione 是 delta 9,11 类固醇类合成的中间体，如 Vamorolone (HY-109017)。delta 9,11 类固醇是糖皮质激素的修饰产物，具有抗炎特性，并可用作保护细胞免受脂质过氧化和抑制新生血管形成的试剂。

体外研究 Δ9,11 衍生物被设计用于稳定地结合到细胞膜中并抑制脂质过氧化，而不表现出类固醇或矿质甾醇活性，从而避免了传统皮质激素相关的副作用。VBP15 作为先导化合物，因其强大的 NF-κB 抑制和 GR 转位作用类似于泼尼松和地塞米松、缺乏转激活特性以及良好的生物利用度而被选中。

用途 醋酸四烯物还是地塞米松、倍他米松和确炎舒松等药物的中间体。

反应信息

• 作为反应物：
  描述：

  2-((10S,13S)-10,13-dimethyl-3-oxo-6,7,8,10,12,13,14,15-octahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl acetate 在 过氧乙酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 、 甲苯 为溶剂， 生成 (10S,13S,16R,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,10,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one
  参考文献：
  名称：

  VBP15: Preclinical characterization of a novel anti-inflammatory delta 9,11 steroid

  摘要：

  Delta 9,11 modifications of glucocorticoids (21-aminosteroids) have been developed as drugs for protection against cell damage (lipid peroxidation; lazaroids) and inhibition of neovascularization (anecortave). Part of the rationale for developing these compounds has been the loss of glucocorticoid receptor binding due to the Delta 9,11 modification, thus avoiding many immunosuppressive activities and deleterious side effect profiles associated with binding to glucocorticoid and mineralocorticoid receptors. We recently demonstrated that anecortave acetate and its 21-hydroxy analog (VBP1) do, in fact, show glucocorticoid and mineralocorticoid receptor binding activities, with potent translocation of the glucocorticoid receptor to the cell nucleus. We concluded that Delta 9,11 steroids showed novel anti-inflammatory properties, retaining NF-kappa B inhibition, but losing deleterious glucocorticoid side effect profiles. Evidence for this was developed in pre-clinical trials of chronic muscle inflammation. Here, we describe a drug development program aimed at optimizing the Delta 9,11 chemistry. Twenty Delta 9,11 derivatives were tested in in vitro screens for NF-kappa B inhibition and GR translocation to the nucleus, and low cell toxicity. VBP15 was selected as the lead compound due to potent NF-kappa B inhibition and GR translocation similar to prednisone and dexamethasone, lack of transactivation properties, and good bioavailability. Phamacokinetics were similar to traditional glucocorticoid drugs with terminal half-life of 0.35 h (mice), 0.58 h (rats), 5.42 h (dogs), and bioavailability of 74.5% (mice), and 53.2% (dogs). Metabolic stability showed >= 80% remaining at 1 h of VBP6 and VBP15 in human, dog, and monkey liver microsomes. Solubility, permeability and plasma protein binding were within acceptable limits. VBP15 moderately induced CYP3A4 across the three human hepatocyte donors (24-42%), similar to other steroids. VBP15 is currently under development for treatment of Duchenne muscular dystrophy. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.009
• 作为产物：
  描述：

  acetic acid 2-((10R,11S,13S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15-decahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl ester 在 4-二甲氨基吡啶 、 N-氯代丁二酰亚胺 、 sulfur(IV) oxide * pyridine 作用下， 以 吡啶 为溶剂， 以98.6 %的产率得到2-((10S,13S)-10,13-dimethyl-3-oxo-6,7,8,10,12,13,14,15-octahydro-3H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl acetate
  参考文献：
  名称：

  CN115536718

  摘要：

  公开号：

文献信息

• PROCESS FOR THE PREPARATION OF FLUOROTETRAENE
  申请人：Ferrino Sergio

  公开号：US20080234506A1

  公开（公告）日：2008-09-25

  There is provided a process for preparing 21-acetyloxy-6-alpha-fluoro-pregna-1,4,9(11),16-tetraene-3,20-dione compound of Formula I, which comprises reacting 21-acetyloxy-pregna-1,3,5,9(11),16-pentaene-3-oxo acetate with a fluorinating agent.

  提供了一种制备Formula I中的21-乙酰氧基-6-α-氟孕甾-1,4,9(11),16-四烯-3,20-二酮化合物的过程，该过程包括将21-乙酰氧基-孕甾-1,3,5,9(11),16-五烯-3-酮醋酸酯与氟化剂反应。
• [EN] NOVEL PROCESS FOR PREPARATION OF GLUCOCORTICOID STEROIDS<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE STÉROÏDES DE TYPE GLUCOCORTICOÏDE
  申请人：CORAL DRUGS PVT LTD

  公开号：WO2016120891A1

  公开（公告）日：2016-08-04

  The present invention discloses a process for the preparation of 16, 17-acetals of pregnane derivatives having formula (I) wherein each substituent is independently selected from; R1 is H or CH3; R2 is C1-C6 linear or branched alkyl, alkynyl group or cycloalkyl group; aryl or heteroaryl group; or R1 and R2 combine to form saturated, unsaturated C3-C6 cyclic or heterocyclic ring; R3 and R4 are same or different and each independently represents H or halogen; R5 is -OH or –OCOR wherein R represents H or C1-C6 linear, branched or cyclic alkyl group that may be substituted.

  本发明揭示了一种制备16,17-孕烷衍生物的16,17-缩醛的方法，其具有式(I)的结构，其中每个取代基独立地选择自; R1为H或CH3; R2为C1-C6直链或支链烷基，炔基或环烷基; 芳基或杂环芳基; 或R1和R2结合形成饱和的、不饱和的C3-C6环或杂环环; R3和R4相同或不同，每个独立地表示H或卤素; R5为-OH或-OCOR，其中R表示H或C1-C6直链、支链或环烷基，可能被取代。
• AQUEOUS ORAL PHARMACEUTICAL SUSPENSION COMPOSITIONS
  申请人：ReveraGen BioPharma, Inc.

  公开号：US20200281942A1

  公开（公告）日：2020-09-10

  Provided is an aqueous oral pharmaceutical suspension composition comprising vamorolone Form I. Also provided are methods for its preparation and its use.

  提供的是含有vamorolone Form I的水性口服药用悬浮液组成。同时提供了其制备方法和用途。
• Non-hormonal steroid modulators of NF-κβ for treatment of disease
  申请人：Reveragen Biopharma, Inc.

  公开号：US10464967B2

  公开（公告）日：2019-11-05

  The present invention relates to compounds and methods which may be useful as treatments of diseases.

  本发明涉及可能用作疾病治疗的化合物和方法。
• NON-HORMONAL STEROID MODULATORS OF NF-KAPPA BETA FOR TREATMENT OF DISEASE
  申请人：Reveragen Biopharma, Inc.

  公开号：US20160375037A1

  公开（公告）日：2016-12-29

  The present invention relates to compounds and methods which may be useful as treatments of diseases.

  本发明涉及化合物和方法，可用作治疗疾病的治疗方法。