17β-<(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)oxy>androst-4-en-3-one | 89648-34-0

• 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: 17β-<(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)oxy>androst-4-en-3-one
• 英文别名: 17β-[(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)oxy]androst-4-en-3-one；17β-[(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)oxy]androst-4-en-3-on；[(8R,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl] 1-methyl-4H-pyridine-3-carboxylate
• CAS: 89648-34-0
• 化学式: C₂₆H₃₅NO₃
• 分子量: 409.569
• InChiKey: YLCIAAIJXPZBEJ-IXKNJLPQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  17β-<(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)oxy>androst-4-en-3-one 在 citrate phosphate dextrose 、 plasma 作用下， 以 水 、 二甲基亚砜 为溶剂， 生成 17β-<(1-methyl-3-pyridiniumcarbonyl)oxy>androst-4-en-3-one iodide
  参考文献：
  名称：

  通过生物膜XIV改善递送：使用氧化还原化学递送系统，特定于大脑的睾丸激素持续递送

  摘要：

  平衡吡啶鎓盐氧化还原递送系统中的二氢吡啶用于脑中睾丸激素的特异性递送和持续释放。在雌性大鼠中施用睾丸激素的N-甲基-1,4-二氢烟酸酯使大脑中相应的季铵盐，睾丸激素三扁桃酸酯高水平且持续存在。与此形成鲜明对比的是，它被迅速从普通流通中排除。随着季盐持续释放，睾丸激素“锁定”在大脑中，t1 / 2 = 20小时。

  DOI：

  10.1002/jps.2600730324
• 作为产物：
  描述：

  17-beta-羟基雄甾-4-烯-3-酮烟酸酯 在 sodium dithionite 、 碳酸氢钠 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 0.33h， 生成 17β-<(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)oxy>androst-4-en-3-one
  参考文献：
  名称：

  通过生物膜XIV改善递送：使用氧化还原化学递送系统，特定于大脑的睾丸激素持续递送

  摘要：

  平衡吡啶鎓盐氧化还原递送系统中的二氢吡啶用于脑中睾丸激素的特异性递送和持续释放。在雌性大鼠中施用睾丸激素的N-甲基-1,4-二氢烟酸酯使大脑中相应的季铵盐，睾丸激素三扁桃酸酯高水平且持续存在。与此形成鲜明对比的是，它被迅速从普通流通中排除。随着季盐持续释放，睾丸激素“锁定”在大脑中，t1 / 2 = 20小时。

  DOI：

  10.1002/jps.2600730324

文献信息

• Brain-specific drug delivery
  申请人：University of Florida

  公开号：US04540564A1

  公开（公告）日：1985-09-10

  The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are: (a) compounds of the formula [D-DHC] (I) wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine .revreaction. pyridinium salt redox carrier, with the proviso that when [DHC] is ##STR1## wherein R is lower alkyl or benzyl and [D] is a drug species containing a single NH.sub.2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH.sub.2 or OH functional group to the carbonyl function of [DHC], then [D] must be other than a sympathetic stimulant, steroid sex hormone or long chain alkanol; and (b) non-toxic pharmaceutically acceptable salts of compounds of formula (I) wherein [D] is a centrally acting drug species and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine .revreaction. pyridinium salt redox carrier. The corresponding ionic pyridinium salt type drug/carrier entities [D-QC].sup.+ Y.sup.- are also disclosed.

  这些适用于特定部位/持续向大脑释放中枢作用药物的主体化合物是：(a) 公式[D-DHC]（I）的化合物，其中[D]是中枢作用药物，[DHC]是一种还原的、可生物氧化的、能穿透血脑屏障的脂溶性二氢吡啶.revreaction.吡啶盐氧化还原载体的形式，但当[DHC]是##STR1## 其中R是较低的烷基或苄基，[D]是含有单个NH.sub.2或OH官能团的药物种类，当存在单个OH官能团时，该OH官能团为初级或次级OH官能团，所述的药物种类直接通过所述的NH.sub.2或OH官能团与[DHC]的羰基功能连接，那么[D]必须不是交感神经刺激剂、甾体性激素或长链烷醇；以及(b) 公式（I）的化合物的无毒、药学上可接受的盐，其中[D]是中枢作用药物，[DHC]是一种还原的、可生物氧化的、能穿透血脑屏障的脂溶性二氢吡啶.revreaction.吡啶盐氧化还原载体的形式。还披露了相应的离子吡啶盐型药物/载体实体[D-QC].sup.+ Y.sup.-。
• Testicular-specific drug delivery
  申请人：University of Florida

  公开号：US04622218A1

  公开（公告）日：1986-11-11

  Testicularly acting drug species are site-specifically/sustainedly delivered to the testes by administering to a male in need of such treatment a pharmacologically effective amount of the target drug species [D] tethered to a reduced, blood-testis barrier penetrating lipoidal form [D--DHC] of a dihydropyridine.revreaction.pyridinium salt type redox carrier, e.g. 1,4-dihydrotrigonelline. Oxidation of the dihydropyridine carrier moiety in vivo to the ionic pyridinium salt type drug/carrier entity [D--QC].sup.+ prevents elimination thereof from the testes, while elimination from the general circulation is accelerated, resulting in significant and prolongedly sustained testicular-specific drug activity, whether ascribable to the cleavage of the [D--QC].sup.+ entity and sustained release of the drug [D] in the testes and/or to [D--QC].sup.+ itself.

  睾丸作用药物种类通过给需要此类治疗的男性施用目标药物种类[D]的药理有效量，将其定向/持续地传递到睾丸。所使用的是一种还原的、穿透血睾障壁的脂质形式[D--DHC]的二氢吡啶.叠氮盐型氧化还原载体，例如1,4-二氢三甲基咖啡碱。体内二氢吡啶载体基团氧化为离子型叠氮盐型药物/载体实体[D--QC].sup.+，防止其从睾丸中被排除，同时加速其从一般循环中的排除，导致显著且持续时间较长的睾丸特异性药物活性，无论是归因于[D--QC].sup.+实体的裂解和药物[D]在睾丸中的持续释放，还是[D--QC].sup.+本身。
• Method for treating male sexual dysfunction
  申请人：UNIVERSITY OF FLORIDA

  公开号：EP0256668A2

  公开（公告）日：1988-02-24

  The invention provides the use of a compound of the formula or a non-toxic pharmaceutically acceptable salt thereof, wherein [E] is an estrogen and [DHC] is the reduced, biooxidizable, blood-brain barrier-penetrating, lipoidal form of a dihydropyridine pyridinium salt redox carrier in the preparation of a medicament for treating male sexual dysfunction. Compositions for use in the subject method are also disclosed. A preferred compound for use in the method and compositions is an estradiol derivative, namely, 17β-[(1-methyl-1,4-dihydro-3-pyridinyl)carbonyloxy]estra-1,3,5(1O)-trien-3-ol.

  本发明提供了式化合物或其无毒药学上可接受的盐在制备治疗男性性功能障碍的药物中的用途，其中[E]是雌激素，[DHC]是二氢吡啶吡啶盐氧化还原载体的还原型、生物可氧化型、血脑屏障穿透型、脂质型。 还公开了用于所述方法的组合物。 用于所述方法和组合物的优选化合物是雌二醇衍生物，即17β-[(1-甲基-1,4-二氢-3-吡啶基)羰基氧基]雌甾-1,3,5(1O)-三烯-3-醇。
• Redox systems for brain-targeted drug delivery
  申请人：UNIVERSITY OF FLORIDA

  公开号：EP0327766A2

  公开（公告）日：1989-08-16

  Inclusion complexes of hydroxypropyl, hydroxyethyl, glucosyl, maltosyl or maltotriosyl derivatives of β- or γ-cyclodextrin with the reduced, biooxidizable, blood-brain barrier penetrating, lipoidal forms of dihydropyridine = pyridinium salt redox systems for brain-targeted drug delivery provide a means for stabilizing the redox systems, particularly against oxidation. The redox inclusion complexes also provide a means for decreasing initial drug concentrations in the lungs after administration of the systems, leading to decreased toxicity. In selected instances, complexation results in substantially improved water solubility of the redox systems as well.

  β-或γ-环糊精的羟丙基、羟乙基、葡糖基、麦芽糖基或麦芽三糖基衍生物与还原型、可生物氧化、可穿透血脑屏障、类脂形式的二氢吡啶＝吡啶鎓盐氧化还原体系的包合物为脑靶向给药提供了一种稳定氧化还原体系，特别是防止氧化的方法。氧化还原包合物还能降低给药后肺部的初始药物浓度，从而降低毒性。在某些情况下，络合物还能大大提高氧化还原体系的水溶性。
• Cyclodextrin complexation
  申请人：CYCLOPS h.f.

  公开号：EP0579435A1

  公开（公告）日：1994-01-19

  The invention provides a method for enhancing the complexation of a cyclodextrin with a lipophilic and/or water-labile drug, comprising combining from about 0.1 to about 70% (weight/volume) of a cyclodextrin and from about 0.001 to about 5% (weight/volume) of a pharmaceutically acceptable, pharmacologically inactive, water-soluble polymer in an aqueous medium, the polymer and cyclodextrin being dissolved in the aqueous medium before the drug is added, the aqueous medium which comprises the polymer and cyclodextrin being maintained at from about 30 to about 150°C for a period of from about 0.1 to about 100 hours before, during and/or after the drug is added, optionally followed by removal of water. Related methods, co-complexes of drug/cyclodextrin/polymer, pharmaceutical compositions and cyclodextrin/polymer complexing agents are also provided. Analogous methods, co-complexes and compositions in which the drug is replaced with a food additive, cosmetic additive or agrochemical are also described.

  本发明提供了一种增强环糊精与亲脂性和/或水溶性药物复配的方法，包括将约 0.1%至约 70%（重量/体积）的环糊精和约 0.001至约5%（重量/体积）的药学上可接受的、药理上无活性的水溶性聚合物在水介质中，聚合物和环糊精在添加药物之前溶解在水介质中，包含聚合物和环糊精的水介质在添加药物之前、期间和/或之后在约30至约150°C的温度下保持约0.1至约100小时，可选地随后除去水。还提供了相关的方法、药物/环糊精/聚合物的共复合物、药物组合物和环糊精/聚合物复配剂。此外，还介绍了用食品添加剂、化妆品添加剂或农用化学品替代药物的类似方法、共混物和组合物。