3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one | 162882-64-6

• 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: 3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one
• 英文别名: 1-[(3R,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-3-(methoxymethyl)-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]ethanone
• CAS: 162882-64-6
• 化学式: C₂₃H₃₈O₃
• 分子量: 362.553
• InChiKey: FVIBFMBTKOCWJO-NWWWSWJSSA-N

物化性质

• 熔点：
  154-156 °C
• 沸点：
  459.4±10.0 °C(Predicted)
• 密度：
  1.051±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one 在 氢溴酸 、 溴 、 lithium hydride 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.5h， 生成 3α-hydroxy-21-(1'-imidazolyl)-3β-methoxymethyl-5α-pregnan-20-one
  参考文献：
  名称：

  Synthesis of 3α-hydroxy-21-(1′-imidazolyl)-3β-methoxyl-methyl-5α-pregnan-20-one via lithium imidazole with 17α-acetylbromopregnanone

  摘要：

  The synthesis of biologically active 3 alpha-hydroxyl-21-(1'-imidazolyl)-3 beta-methoxymethyl-5 alpha-pregnan-20-one (11) was accomplished in six steps. The key steps were the improvement of stereoselectivity for acetyl isomers in C-17 and the introduction of imidazole into the core structure by use of lithium imidazole. This latter key step provided the desired product 11 in 82% yield without the formation of 1,3-disubstituted imidazolium salt as impurity, which is generally observed in traditional method. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.08.006
• 作为产物：
  描述：

  孕烯醇酮 在 palladium on activated charcoal sodium hydroxide 、 sodium hypochlorite 、 potassium tert-butylate 、 氢气 、 sodium bromide 作用下， 以 四氢呋喃 、 水 、 溶剂黄146 、 二甲基亚砜 为溶剂， 20.0~60.0 ℃ 、413.68 kPa 条件下， 反应 25.0h， 生成 3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one
  参考文献：
  名称：

  Synthesis of 3α-hydroxy-21-(1′-imidazolyl)-3β-methoxyl-methyl-5α-pregnan-20-one via lithium imidazole with 17α-acetylbromopregnanone

  摘要：

  The synthesis of biologically active 3 alpha-hydroxyl-21-(1'-imidazolyl)-3 beta-methoxymethyl-5 alpha-pregnan-20-one (11) was accomplished in six steps. The key steps were the improvement of stereoselectivity for acetyl isomers in C-17 and the introduction of imidazole into the core structure by use of lithium imidazole. This latter key step provided the desired product 11 in 82% yield without the formation of 1,3-disubstituted imidazolium salt as impurity, which is generally observed in traditional method. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.08.006

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS<br/>[FR] COMPOSITIONS ET MÉTHODES POUR TRAITER DES TROUBLES DU SNC
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2016061527A1

  公开（公告）日：2016-04-21

  Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein (II), A, R1, R2, R3a, R4a, R4b, R5, R7a, and R7b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

  本文描述了式(I)的神经活性类固醇，或其药用可接受盐；其中(II)，A，R1，R2，R3a，R4a，R4b，R5，R7a和R7b如本文所定义。在某些实施例中，这些化合物被设想为GABA调节剂。本发明还提供了包括本发明化合物的药物组合物，以及使用和治疗方法，例如用于诱导镇静和/或麻醉。
• 3Alpha-hydroxy-3beta-methoxymethyl-substituted steroids and the use thereof
  申请人：Euro-Celtique S.A.

  公开号：US20040034002A1

  公开（公告）日：2004-02-19

  This invention relates to compounds having the Formula I: 1 or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein: R 1 is H or methyl; R 2 is 5&agr;- or 5&bgr;-H; R 3 is an optionally substituted N-attached heteroaryl group or a group —X—R 4 ; R 4 is an optionally substituted carbon-attached heteroaryl group; and X is O, S or N. The invention also is directed to the use of 3&agr;-hydroxy-3&bgr;-methoxymethyl-substituted steroids as sedative/hypnotics and for inducing anesthesia.

  本发明涉及具有以下式I的化合物：1或其药学上可接受的盐，前药或溶剂，其中：R1为H或甲基；R2为5α-或5β-H；R3为可选取代的N-连接的杂环芳基团或群体—X—R4；R4为可选取代的碳连接的杂环芳基团；X为O、S或N。本发明还涉及使用3α-羟基-3β-甲氧甲基取代的类固醇作为镇静催眠剂和诱导麻醉剂。
• [EN] 3 alpha -HYDROXY-3 beta METHOXYMETHYL-21-HETEROCYCLE SUBSTITUTED STEROIDS WITH ANESTHETIC ACTIVITY<br/>[FR] STEROIDES SUBSTITUES PAR HETEROCYCLE 3ALPHA-HYDROXY-3BETA-METHOXYMETHYL-21- AYANT UN POUVOIR ANESTHESIQUE
  申请人：COCENSYS INC

  公开号：WO2000066614A1

  公开（公告）日：2000-11-09

  This invention relates to compounds having Formula (I) or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein; R1 is H or methyl; R2 is 5α- or 5β- H; R3 is an optionally substituted N-attached heteroaryl group or a group -X-R4; R4 is an optionally substituted carbon-attached heteroaryl group; and X is O, S or N. The invention also is directed to the use of 3α- hydroxy-3β- methoxymethyl-substituted steroids as sedative/hypnotics and for inducing anesthesia.

  本发明涉及具有式（I）或其药学上可接受的盐，前药或溶剂的化合物，其中：R1为H或甲基；R2为5α-或5β-H；R3为可选取代的N-连接杂环基团或-X-R4基团；R4为可选取代的碳连接杂环基团；X为O、S或N。本发明还涉及将3α-羟基-3β-甲氧甲基取代的类固醇用作镇静催眠剂和诱导麻醉的用途。
• [EN] ANDROSTANE AND PREGNANE SERIES FOR ALLOSTERIC MODULATION OF GABA RECEPTOR<br/>[FR] SERIES DE L'ANDROSTANE ET DE LA PREGNANE PRODUISANT UNE MODULATION ALLOSTERIQUE DU RECEPTEUR DU GABA
  申请人：COCENSYS, INC.

  公开号：WO1996016076A1

  公开（公告）日：1996-05-30

  (EN) Methods, compositions, and compounds for modulating the GABAA receptor-chloride ionophore complex to alleviate stress, anxiety, seizures, mood disorders, PMS and PND and to induce anesthesia.(FR) Procédés, compositions et composés servant à moduler le complexe ionophore de chlorure et récepteur du GABAA, permettant ainsi d'atténuer le stress, l'anxiété, les crise d'épilepsie, les troubles de l'humeur, la dépression post natale et le syndrome prémenstruel, et de provoquer l'anesthésie.

  (中文) 用于调节GABAA受体-氯离子复合物以缓解压力、焦虑、癫痫、情绪障碍、PMS和PND并诱导麻醉的方法、组合物和化合物。
• 3-Alpha-hydroxy 21-n-heteroaryl-pregnane derivatives for modulation of brain excitability and a process for the production thereof
  申请人：Chang Ping W.

  公开号：US20090118248A1

  公开（公告）日：2009-05-07

  The invention relates to a novel multi step process of making compounds of Formula I: wherein R 1 is an alkoxy group and R 2 is an optionally substituted, N-attached heteroaryl. The hydrogen at the 5-position can be α or β isomer, preferably α. Preferably the compound of Formula I is 17β isomer. The invention also relates to novel 3α-hydroxy-3β-substituted-17-substituted steroid compounds having GABA A receptor modulating activity, pharmaceutical compositions comprising these compounds, and the use of these compounds in a method of modulating brain excitability.

  本发明涉及一种制备公式I化合物的新型多步骤过程：其中R1是烷氧基，R2是可选择性取代的、N-连接的杂环芳基。5位氢可以是α或β异构体，优选为α。优选的公式I化合物是17β异构体。本发明还涉及具有GABAA受体调节活性的新型3α-羟基-3β-取代-17-取代类固醇化合物、包含这些化合物的制药组合物以及使用这些化合物调节脑兴奋性的方法。