3α-hydroxy-17β-methoxy-5α-androstane | 75246-13-8

• 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: 3α-hydroxy-17β-methoxy-5α-androstane
• 英文别名: 3alpha-Hydroxy-17beta-methoxy-5alpha-androstane；(3R,5S,8R,9S,10S,13S,14S,17S)-17-methoxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol
• CAS: 75246-13-8
• 化学式: C₂₀H₃₄O₂
• 分子量: 306.489
• InChiKey: DJCLLPRQXAXWAB-RGJFDMQWSA-N

物化性质

• 熔点：
  146 °C(Solv: methanol (67-56-1))
• 沸点：
  399.4±15.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3α-hydroxy-17β-methoxy-5α-androstane 在 N-氯代丁二酰亚胺 作用下， 生成 3β-Chloro-17β-methoxy-5α-androstane
  参考文献：
  名称：

  Male contraceptive steroids and methods of use

  摘要：

  本发明的类固醇在口服时被发现可作为男性避孕药物。停止使用本发明的男性避孕类固醇后，男性很快恢复正常生育能力。

  公开号：

  US04297350A1
• 作为产物：
  描述：

  (3R,5S,8R,9S,10S,13S,14S)-3-(methoxymethoxy)-10,13-dimethylHexadecahydro- 17H-cyclopenta[a]phenanthren-17-one 在 sodium tetrahydroborate 、 sodium hydride 、 乙酰氯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 mineral oil 为溶剂， 反应 7.0h， 生成 3α-hydroxy-17β-methoxy-5α-androstane
  参考文献：
  名称：

  10.1111/bph.16490

  摘要：

  AbstractBackground and PurposeNeurosteroids are allosteric modulators of GABAA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady‐state binding affinities of various neurosteroids for specific sites on the GABAA receptor.Experimental ApproachTwo methods were developed to measure neurosteroid binding affinity: (1) quenching of specific tryptophan residues in neurosteroid binding sites by the neurosteroid 17‐methylketone group, and (2) FRET between MQ290 (an intrinsically fluorescent neurosteroid) and tryptophan residues in the binding sites. The assays were developed using ELIC‐α1GABAAR, a chimeric receptor containing transmembrane domains of the α1‐GABAA receptor. Tryptophan mutagenesis was used to identify specific interactions.Key ResultsAllopregnanolone (3α‐OH neurosteroid) was shown to bind at intersubunit and intrasubunit sites with equal affinity, whereas epi‐allopregnanolone (3β‐OH neurosteroid) binds at the intrasubunit site. MQ290 formed a strong FRET pair with W246, acting as a site‐specific probe for the intersubunit site. The affinity and site‐specificity of several neurosteroid agonists and inverse agonists was measured using the MQ290 binding assay. The FRET assay distinguishes between competitive and allosteric inhibition of MQ290 binding and demonstrated an allosteric interaction between the two neurosteroid binding sites.Conclusions and ImplicationsThe affinity and specificity of neurosteroid binding to two sites in the ELIC‐α1GABAAR were directly measured and an allosteric interaction between the sites was revealed. Adaptation of the MQ290 FRET assay to a plate‐reader format will enable screening for high affinity agonists and antagonists for neurosteroid binding sites.

  DOI：

  10.1111/bph.16490

文献信息

• Conformationally Constrained Anesthetic Steroids That Modulate GABA_A Receptors
  作者：Alison Anderson、Andrew C. Boyd、John K. Clark、Lee Fielding、David K. Gemmell、Niall M. Hamilton、Maurice S. Maidment、Valerie May、Ross McGuire、Petula McPhail、Francis H. Sansbury、Hardy Sundaram、Robert Taylor

  DOI：10.1021/jm000977e

  日期：2000.11.1

  alpha-hydroxyandrostane derivatives bearing a conformationally constrained hydrogen-bonding moiety were prepared. Their anesthetic potency and their binding affinity for GABA(A) receptors, measured by intravenous administration to mice and inhibition of [(35)S]TBPS binding to rat whole brain membranes, were compared with that of known anesthetic 3 alpha-hydroxypregnan-20-ones. Synthetic steroids with similar

  制备了各种带有构象约束的氢键部分的环状醚和其他3个α-羟基雄烷衍生物。将它们的麻醉力和对GABA（A）受体的结合亲和力与已知的麻醉药3α-hydroxypregnan-20进行了比较，这些麻醉剂是通过对小鼠静脉内给药以及对[（35）S] TBPS与大鼠全脑膜结合的抑制作用来测量的-那些。具有与内源性3α-羟基pregnan-20-one相似的体外和体内活性的合成类固醇在类固醇D环的β面上均带有醚氧。这些结果表明，为实现最佳的GABA（A）受体调节，接受氢键的取代基应垂直于类固醇的β面上的D环平面。
• NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME
  申请人：Sage Therapeutics, Inc.

  公开号：US20140235600A1

  公开（公告）日：2014-08-21

  The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

  本公开涉及神经活性的19-烷氧基-17-取代类固醇，以及其药学上可接受的盐，例如用作麻醉剂和/或治疗与GABA功能和活性有关的疾病。本公开还涉及包含这些化合物的制药组合物。
• Neuroactive 3.alpha.-hydroxy-steroids of the androstane and pregnane series
  申请人：Purdue Pharma Ltd.

  公开号：EP1288220A2

  公开（公告）日：2003-03-05

  The invention relates to a 3α-hydroxy, 17-(un)substituted derivatives of the androstane series and 3α-hydroxy, 21-substituted derivatives of the pregnane series. These derivatives are capable of acting at the recently identified site on the GRC, thereby modulating brain excitability in a manner that will alleviate stress, anxiety, insomnia, mood disorders that are amenable to GRC-active agents (such as depression) and seizure activity. The steroid derivatives of this invention are those having general structural formula (I), wherein R, R1, R2, R3,R4, R5, R6, R7, R8, R9 and R10 are further defined herein and the dotted lines are single or double bonds. The structure includes androstanes pregnanes (R4 = methyl), 19-norandrostanes, and norpregnanes (R4=H).

  本发明涉及一种 3α-羟基、17-（未）取代的雄甾烷系列衍生物和 3α-羟基、21-取代的孕烷系列衍生物。这些衍生物能够作用于最近确定的 GRC 上的位点，从而调节大脑的兴奋性，从而缓解压力、焦虑、失眠、适合 GRC 活性剂的情绪紊乱（如抑郁症）和癫痫发作活动。本发明的类固醇衍生物是具有通式（I）的衍生物，其中 R、R1、R2、R3、R4、R5、R6、R7、R8、R9 和 R10 在此进一步定义，虚线为单键或双键。该结构包括雄甾烷基孕烷（R4=甲基）、19-去雄甾烷基孕烷和去孕烷（R4=H）。
• GRIECO, PAUL A.;STUK, TIMOTHY L., J. AMER. CHEM. SOC., 112,(1990) N1, C. 7799-7801
  作者：GRIECO, PAUL A.、STUK, TIMOTHY L.

  DOI：——

  日期：——
• NEUROACTIVE STEROIDS OF THE ANDROSTANE AND PREGNANE SERIES
  申请人：Cocensys, Inc.

  公开号：EP0837874A2

  公开（公告）日：1998-04-29