19-(tetrahydropyran-2'-yl-oxy)-androst-4-ene-3,17-dione | 2300-64-3

• 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: 19-(tetrahydropyran-2'-yl-oxy)-androst-4-ene-3,17-dione
• 英文别名: 19-Tetrahydropyranyloxy-4-androstene-3,17-dione；(8R,9S,10S,13S,14S)-13-methyl-10-(oxan-2-yloxymethyl)-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 2300-64-3
• 化学式: C₂₄H₃₄O₄
• 分子量: 386.532
• InChiKey: NTBVWEHHGYJMDB-BTQIHSFSSA-N

物化性质

• 熔点：
  125 °C
• 沸点：
  542.8±50.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  19-(tetrahydropyran-2'-yl-oxy)-androst-4-ene-3,17-dione 在 氨 、 lithium 、 氯化铵 、 对甲苯磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 5.58h， 生成 19-hydroxydihydrotestosterone
  参考文献：
  名称：

  3-脱氧雄激素的合成及化学模型反应研究：证据支持人类胎盘芳香化酶催化2、3-烯醇化假说

  摘要：

  许多迄今未描述的Δ 2 -和Δ 3 -3脱氧5α雄激素衍生物（17β，19-二醇12和13，19-羟基-17-酮16和17，19氧代-17-酮18和19）以高收率合成。锂-氨还原的19-（四氢吡喃-2-基氧基）雄甾-4-烯-3- -3,17-二酮7接着夏皮罗反应允许易于施工两个Δ的2 -和Δ 3 -3脱氧5α类固醇系统。已知的Δ的改进的合成4 -3- deoxyandrogen衍生物（28，30，31）以高产量完成。19位羟基的掩蔽，以产生Δ是必要4以良好的收率-3- deoxyandrogen系统，在对比的是帐户化合物的早期合成的28和30通过Numazawa。在芳香动作第三氧化处理的化学模型进行反应与Δ 2 - ，Δ 3 - ，Δ 4 -和Δ 2,4 -3-脱氧-19-氧代- 17-酮甾族化合物（18，19，31和5分别）。结果示出了用于两个Δ需要2 -和Δ 4，以便产生Δ-unsat

  DOI：

  10.1039/p19940002237
• 作为产物：
  描述：

  四氢吡喃 、 19-羟基雄甾-4-烯-3,17-二酮 在 4-甲基苯磺酸吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以97.65%的产率得到19-(tetrahydropyran-2'-yl-oxy)-androst-4-ene-3,17-dione
  参考文献：
  名称：

  [EN] NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF
  [FR] STÉROÏDES NEUROACTIFS, LEURS COMPOSITIONS ET UTILISATIONS

  摘要：

  本文描述了化学式（I）的类固醇及其药用盐；其中R1、R2a、R2b、R3、R4、R5a、R5b、R6和Z的定义如本文所述。这些化合物被认为对预防和治疗各种与中枢神经系统相关的疾病有用，例如治疗睡眠障碍、情绪障碍、精神分裂症谱系障碍、癫痫性障碍、记忆和/或认知障碍、运动障碍、人格障碍、自闭症谱系障碍、疼痛、创伤性脑损伤、血管疾病、物质滥用障碍和/或戒断综合征，以及耳鸣症的治疗。

  公开号：

  WO2015195962A1

文献信息

• [EN] NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF<br/>[FR] STÉROÏDES NEUROACTIFS, COMPOSITIONS ET UTILISATIONS
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2015027227A1

  公开（公告）日：2015-02-26

  Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein -------, R1, R2, R5, A and L 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.

  本文描述了化学式（I）中的神经活性类固醇或其药用可接受盐；其中-------，R1，R2，R5，A和L如本文所定义。在某些实施例中，预期这些化合物将表现为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/或麻醉的方法。
• Fragmentierungen und intramolekulare Abstraktionen tertiärer Wasserstoffatome ausgehend von primären Oxyradikalen mit fixierten Reaktionszentren
  作者：D. Hauser、K. Heusler、J. Kalvoda、K. Schaffner、O. Jeger

  DOI：10.1002/hlca.19640470737

  日期：——

  Treated with lead tetraacetate in boiling benzene the saturated 19-hydroxy steroids 9 and 16 gave complex mixtures containing products of fragmentation and of hydrogen abstraction from δ-carbon atoms. This behaviour differs significantly from the preponderantly uniform fragmentation of the unsaturated alcohols 1 and 36, which takes place already at room temperature and is ascribed to anchimeric acceleration

  用四乙酸铅在沸腾的苯中处理，饱和的19-羟基甾族化合物9和16得到复杂的混合物，其中含有裂解和从δ-碳原子提取氢的产物。该行为与不饱和醇1和36的显着均匀的断裂明显不同，该断裂已经在室温下发生，并且归因于通过均烯丙基双键的邻苯二甲酸酯的促进作用。
• 19-Oxygenated-5.alpha.-androstanes for the enhancement of libido
  申请人：Richardson-Merrell Inc.

  公开号：US04071625A1

  公开（公告）日：1978-01-31

  Derivatives of 19-oxygenated-5.alpha.-androstanes are described which are useful in enhancing the libido and related psychic attitudes in mammals.

  本文描述了19-氧化-5α-雄甾烷衍生物，可用于增强哺乳动物的性欲和相关的心理态度。
• Neuroactive steroids, compositions, and uses thereof
  申请人：SAGE THERAPEUTICS, INC.

  公开号：US10246482B2

  公开（公告）日：2019-04-02

  Described herein are steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein R1, R2a, R2b, R3, R4, R5a, R5b, R6, and Z are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

  本文描述了式 (I) 类固醇：及其药学上可接受的盐；其中 R1、R2a、R2b、R3、R4、R5a、R5b、R6 和 Z 如本文所定义。此类化合物可用于预防和治疗各种中枢神经系统相关疾病，例如，治疗睡眠障碍、情绪障碍、精神分裂症谱系障碍、抽搐障碍、记忆和/或认知障碍、运动障碍、人格障碍、自闭症谱系障碍、疼痛、脑外伤、血管疾病、药物滥用障碍和/或戒断综合征以及耳鸣。
• Oxidation of Dihydrotestosterone by Human Cytochromes P450 19A1 and 3A4
  作者：Qian Cheng、Christal D. Sohl、Francis K. Yoshimoto、F.Peter Guengerich

  DOI：10.1074/jbc.m112.390047

  日期：2012.8

  Dihydrotestosterone is a more potent androgen than testosterone and plays an important role in endocrine function. We demonstrated that, like testosterone, dihydrotestosterone can be oxidized by human cytochrome P450 (P450) 19A1, the steroid aromatase. The products identified include the 19-hydroxy- and 19-oxo derivatives and the resulting Delta(1,10)-, Delta(5,10)-, and Delta(9,10)-dehydro 19-norsteroid products (loss of 19-methyl group). The overall catalytic efficiency of oxidation was similar to 10-fold higher than reported for 3 alpha-reduction by 3 alpha-hydroxysteroid dehydrogenase, the major enzyme known to deactivate dihydrotestosterone. These and other studies demonstrate the flexibility of P450 19A1 in removing the 1- and 2-hydrogens from 19-norsteroids, the 2-hydrogen from estrone, and (in this case) the 1-, 5 beta-, and 9 beta-hydrogens of dihydrotestosterone. Incubation of dihydrotestosterone with human liver microsomes and NADPH yielded the 18- and 19-hydroxy products plus the Delta(1,10)-dehydro 19-nor product identified in the P450 19A1 reaction. The 18- and 19-hydroxylation reactions were attributed to P450 3A4, and 18- and 19-hydroxydihydrotestosterone were identified in human plasma and urine samples. The change in the pucker of the A ring caused by reduction of the Delta(4,5) bond is remarkable in shifting the course of hydroxylation from the 6 beta-, 2 beta-, 1 beta-, and 15 beta-methylene carbons (testosterone) to the axial methyl groups (18, 19) in dihydrotestosterone and demonstrates the sensitivity of P450 3A4, even with its large active site, to small changes in substrate structure.