3,21-二羟基孕甾n-20-酮 | 567-02-2

• 物质功能分类: 天然产物 - 甾体化合物
• 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
• 中文名称: 3,21-二羟基孕甾n-20-酮
• 中文别名: 别孕烷-3Β,21-二醇-20-酮；别孕烷-3&Beta,21-二醇-20-酮
• 英文名称: (3β,5α)-3,21-dihydroxypregnan-20-one
• 英文别名: 3β,5α-tetrahydrodeoxycorticosterone；3β,21-dihydroxy-5α-pregnan-20-one；5α-pregnane-3β,21-diol-20-one；3β,21-Dihydroxy-5α-pregnan-20-on；3-beta,5-alpha-TETRAHYDRODEOSOXYCORTICOSTERONE；2-hydroxy-1-[(3S,5S,8R,9S,10S,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
• CAS: 567-02-2；567-03-3；800-10-2；33995-21-0；51548-31-3；108450-73-3；567-01-1
• 化学式: C₂₁H₃₄O₃
• mdl: MFCD00069492
• 分子量: 334.499
• InChiKey: CYKYBWRSLLXBOW-VTBMCCKRSA-N

物化性质

• 熔点：
  >150oC (dec.)
• 溶解度：
  氯仿（微溶）、乙醇（微溶、超声处理）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.952
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 储存条件：
  保存在2至8℃的环境中，需密封并保持干燥。

制备方法与用途

生物活性方面，3α,21-二羟基-5α-孕纳酮（THDOC）是一种内源性神经甾体，并且是GABAA受体的正向调节剂。研究显示，3α,21-二羟基-5α-孕纳酮能够增强神经元对低浓度α4β1δ GABAA 受体的反应。

反应信息

• 作为反应物：
  描述：

  3,21-二羟基孕甾n-20-酮 生成 3β,7β,21-trihydroxy-5α-pregnan-20-one
  参考文献：
  名称：

  类固醇的生物羟基化。

  摘要：

  DOI：

  10.1007/bf02296685
• 作为产物：
  描述：

  21-乙酰氧基孕烯醇酮 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 0.5h， 生成 3,21-二羟基孕甾n-20-酮
  参考文献：
  名称：

  [EN] INHIBITORS OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE FOR TREATING CARDIOVASCULAR AND PULMONARY CONDITIONS
  [FR] INHIBITEURS DE LA GLUCOSE-6-PHOSPHATE DÉSHYDROGÉNASE PERMETTANT DE TRAITER DES AFFECTIONS CARDIOVASCULAIRES ET PULMONAIRES

  摘要：

  本公开提供了用于治疗或预防受试者的心血管疾病和/或相关肺部疾病的方法。在某些实施例中，该方法包括向受试者投予治疗有效量的葡萄糖-6-磷酸脱氢酶（G6PD）抑制剂，或其药用可接受的盐、非盐非晶形态、溶剂合物、多形态、互变异构体或前药。

  公开号：

  WO2018093856A1

文献信息

• Novel Steroid Inhibitors of Glucose 6-Phosphate Dehydrogenase
  作者：Niall M. Hamilton、Martin Dawson、Emma E. Fairweather、Nicola S. Hamilton、James R. Hitchin、Dominic I. James、Stuart D. Jones、Allan M. Jordan、Amanda J. Lyons、Helen F. Small、Graeme J. Thomson、Ian D. Waddell、Donald J. Ogilvie

  DOI：10.1021/jm300317k

  日期：2012.5.10

  Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially

  类固醇DHEA 1的新型衍生物设计，合成并测试了一种已知的G6PD非竞争性抑制剂G6PD抑制这种脱氢酶的能力。鉴定了几种在酶测定中具有约10倍改进的效力的化合物，并且这种改进的活性转化为细胞测定中的功效。用于类固醇抑制G6PD的SAR已得到实质性发展。3β-醇可用3β-H键供体代替，例如磺酰胺，磺酰胺，尿素和氨基甲酸酯。如果存在C-20酮，可以通过用孕烷核替换雄烷核来实现更高的效能。对于pregnan-20-ones，掺入21-羟基通常是有益的。新化合物通常具有良好的理化性质和令人满意的体外DMPK参数。
• Inhibitors of glucose-6-phosphate dehydrogenase for treating cardiovascular and pulmonary conditions
  申请人：ICHOR, LLC.

  公开号：US11185552B2

  公开（公告）日：2021-11-30

  The present disclosure provides for methods of treating or preventing a cardiovascular disorder and/or a related pulmonary disorder in a subject. In certain embodiments, the method comprises administering a therapeutically effective amount of an inhibitor of Glucose-6-phosphate dehydrogenase (G6PD), or a pharmaceutically acceptable salt, non-salt amorphous form, solvate, poly-morph, tautomer or prodrug thereof.

  本公开提供了治疗或预防受试者心血管疾病和/或相关肺部疾病的方法。 在某些实施方案中，该方法包括施用治疗有效量的葡萄糖-6-磷酸脱氢酶（G6PD）抑制剂或其药学上可接受的盐、非盐无定形形式、溶液、多晶型、同系物或原药。
• Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity
  作者：Satoshi Endo、Toshiyuki Matsunaga、Sho Kumada、Airi Fujimoto、Satoshi Ohno、Ossama El-Kabbani、Dawei Hu、Naoki Toyooka、Jun’ichi Mano、Kazuo Tajima、Akira Hara

  DOI：10.1016/j.abb.2012.07.012

  日期：2012.11

  In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)(1) 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and alpha-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5 alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3 beta-hydroxysteroids, showing K-m of 1.3-9.1 mu M and k(cat) of 1.1-7.6 min(-1). The stereospecific reduction was also observed in the metabolism of 5 alpha- and 5 beta-dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3 beta-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate. (C) 2012 Elsevier Inc. All rights reserved.
• Biotransformation of corticosteroids by Penicillium decumbens ATCC 10436
  作者：Herbert L. Holland、Doan H. Nguyen、Nicola M. Pearson

  DOI：10.1016/0039-128x(95)00071-w

  日期：1995.9

  The biotransformation of a series of corticosteroids by the fungus Penicillium decumbens ATCC 10436 has been investigated. Conversion to the corresponding 5 alpha-dihydrosteroid was observed for all the Delta(4)-3-ketosteroids studied with the exception of deoxycorticosterone, which was converted to a Delta(1,4)-diene. Deoxycorticosterone acetate was, however, converted to a 5 alpha-dihydro product concomitant with ester hydrolysis. Other substrates carrying a C-21 acetoxy group were also hydrolyzed to the alcohol. In two cases (resulting from deoxycorticosterone acetate and 11-deoxycortisone) the 5 alpha-3-keto product was further reduced to the 3 beta-alcohol. No reduction of Delta(1,4)-dienes was observed.
• Steroids. LXX.¹ Removal of the 17-Hydroxyl Group from 17α,21-Dihydroxy-20-ketopregnane Derivatives²
  作者：O. Mancera、G. Rosenkranz、Franz Sondheimer

  DOI：10.1021/ja01626a060

  日期：1955.11