estra-1,3,5(10)-trien-17-on-3-yl nicotinate | 104117-66-0

• 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: estra-1,3,5(10)-trien-17-on-3-yl nicotinate
• 英文别名: (8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl nicotinate；estrone nicotinate；3-Nicotinoyloxyestra-1,3,5(10)-trien-17-one；[(8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] pyridine-3-carboxylate
• CAS: 104117-66-0
• 化学式: C₂₄H₂₅NO₃
• 分子量: 375.467
• InChiKey: KNGFXWUCKBYVJE-YOEKFXIASA-N

物化性质

• 熔点：
  207-209 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  547.3±50.0 °C(Predicted)
• 密度：
  1.209±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  estra-1,3,5(10)-trien-17-on-3-yl nicotinate 在 三[3,4-双(三氟甲基)苯基]膦 作用下， 以 氯仿 为溶剂， 反应 36.0h， 生成 (8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl 5-cyanonicotinate
  参考文献：
  名称：

  吡啶的 C3-氰化：亲电子试剂的限制和区域选择性的决定因素

  摘要：

  吡啶的 C3 选择性氰化是通过硼烷催化的吡啶硼氢化、用氰基亲电试剂取代所得二氢吡啶、最后氧化芳构化的串联过程完成的。该方法适用于吡啶类药物的后期氰化反应。

  DOI：

  10.1002/anie.202216894
• 作为产物：
  描述：

  烟酸 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 estra-1,3,5(10)-trien-17-on-3-yl nicotinate
  参考文献：
  名称：

  Synthesis of pyridine-carboxylate derivatives of hydroxysteroids for liquid chromatography–electrospray ionization-mass spectrometry

  摘要：

  Synthesis and liquid chromatography-electrospray ionization-mass spectrometric (LC-ESI-MS) behaviors of the picolinoyl, 6-methylpicolinoyl, nicotinoyl, 2-methoxynicotinoyl and isonicotinoyl derivatives of the hydroxysteroids estrone, estradiol, 3 beta-hydroxyandrost-5en-17-one (dehydroepiandrosterone) and testosterone in positive mode were investigated. Each steroid was converted to the corresponding pyridine-carboxylate derivative by the acyl chloride method or the mixed anhydride method using the corresponding free acids and 2-methyl-6-nitrobenzoic anhydride; in each case, the latter method principally gave a better yield. The pyridine-carboxylate derivative of each steroid exhibited a clear single peak in liquid chromatography with a reversed phase column and CH3CN-0.1% CH3COOH as a mobile phase. The positive-ESI-mass spectra of the picolinoyl, 6-methylpicolinoyl and 2-methoxynicotinoyl derivatives showed a predominance of [M+H](+), whereas [M+H+CH3CN](+) was observed with high intensity in the nicotinoyl and isonicotinoyl derivatives. Even in the case of estradiol, with its two hydroxyl groups, a single charged ion of [M+H](+) or [M+H+CH3CN](+) was observed in the positive-ESI-mass spectrum of each derivative. The results revealed that picolinoyl derivatization is a simple and versatile method suitable for the sensitive and specific determination of hydroxysteroids by LC-ESI-MS (selected reaction monitoring). (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2006.10.005

文献信息

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

  公开号：US04824850A1

  公开（公告）日：1989-04-25

  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 function 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 entitles [D--QC].sup.+ X.sup.- are also disclosed.

  这些适用于将中枢作用药物种类定向/持续释放到大脑的主体化合物是：(a) 公式[D--DHC] (I)的化合物，其中[D]是中枢作用药物种类，[DHC]是二氢吡啶盐氧化还原、穿透血脑屏障的脂质形式，带有二氢吡啶盐氧化还原载体，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官能团为一次或二次OH官能团，该药物种类通过NH.sub.2或OH官能团直接连接到[DHC]的羰基官能团，则[D]不能是交感神经刺激剂、类固醇性激素或长链烷醇；以及(b) 公式(I)的化合物的无毒的药用可接受盐，其中[D]是中枢作用药物种类，[DHC]是二氢吡啶盐氧化还原、穿透血脑屏障的脂质形式，带有二氢吡啶盐氧化还原载体。还披露了相应的离子式吡啶盐型药物/载体[D--QC].sup.+ X.sup.-。
• Direct Synthesis of <i>N</i>-Difluoromethyl-2-pyridones from Pyridines
  作者：Sen Zhou、Xiaoya Hou、Kai Yang、Minjie Guo、Wentao Zhao、Xiangyang Tang、Guangwei Wang

  DOI：10.1021/acs.joc.1c00228

  日期：2021.5.7

  A novel method for the synthesis of N-difluoromethyl-2-pyridones was described. This protocol enables the synthesis of N-difluoromethyl-2-pyridones from readily available pyridines using mild reaction conditions that are compatible with a wide range of functional groups. The preliminary mechanistic study revealed that N-difluoromethylpyridinium salts were the key intermediates to complete this conversion

  描述了一种合成N-二氟甲基-2-吡啶酮的新方法。该方案能够使用温和的反应条件，从易得的吡啶中合成N-二氟甲基-2-吡啶酮，该反应条件与多种官能团相容。初步的机理研究表明，N-二氟甲基吡啶鎓盐是完成该转化的关键中间体。
• Metal-Free Difunctionalization of Pyridines: Selective Construction of <i>N</i>-CF₂H and <i>N</i>-CHO Dihydropyridines
  作者：Sen Zhou、Ze-Ying Sun、Kongying Zhu、Wentao Zhao、Xiangyang Tang、Minjie Guo、Guangwei Wang

  DOI：10.1021/acs.orglett.1c00352

  日期：2021.3.19

  N-difluoromethylpyridinium salts is seldom explored because of their instability and low availability. Here we present a novel nucleophilic addition of N-difluoromethylpyridinium salts with nitroalkanes to synthesize N-CF2H-dihydropyridines and N-CHO-dihydropyridines in a highly efficient and regioselective pathway. This protocol exhibits good functional group tolerance and good to excellent yields.

  由于N-二氟甲基吡啶鎓盐的不稳定性和低可用性，因此很少对其进行研究。在这里，我们介绍了一种新型的N-二氟甲基吡啶鎓盐与硝基烷的亲核加成，以高效且区域选择性的途径合成N -CF 2 H-二氢吡啶和N -CHO-二氢吡啶。该协议显示出良好的官能团耐受性和良好的优良率。
• Brain-specific drug delivery of steroid sex hormones cleaved from
  申请人：University of Florida

  公开号：US04900837A1

  公开（公告）日：1990-02-13

  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 function 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 entitles [D--QC].sup.+ X.sup.- are also disclosed.

  这些化合物适用于特定部位/持续性地将中枢神经系统药物物种传递到大脑，其中包括：（a）公式[D--DHC]（I）的化合物，其中[D]是中枢神经系统药物物种，[DHC]是二氢吡啶盐氧化还原载体的还原、可生物氧化、穿过血脑屏障的脂质形式，但当[DHC]为##STR1##其中R为低级烷基或苄基，[D]为含有单个NH.sub.2或OH官能团的药物物种，当存在单个OH官能团时，其为一级或二级OH官能团，该药物物种通过NH.sub.2或OH功能团直接连接到[DHC]的羰基功能团，则[D]必须不是交感神经兴奋剂、类固醇性激素或长链烷醇；以及（b）公式（I）的化合物的非毒性药用可接受盐，其中[D]是中枢神经系统药物物种，[DHC]是二氢吡啶盐氧化还原载体的还原、可生物氧化、穿过血脑屏障的脂质形式。还公开了相应的离子吡啶盐型药物/载体[D--QC].sup.+ X.sup.-。
• Method for treating male sexual dysfunction
  申请人：University of Florida

  公开号：US04863911A1

  公开（公告）日：1989-09-05

  The invention provides a method for treating sexual dysfunction in male mammals using a compound of the formula [E--DHC] (I) 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 dihydropridine.revreaction.pyridinium salt redox carrier. 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, 17.beta.-[(1-methyl-1,4-dihydro-3-pyridinyl)carbonyloxy]estra-1,3,5(10)-tr ien-3-ol.

  本发明提供了一种治疗雄性哺乳动物性功能障碍的方法，使用式[E-DHC]（I）的化合物或其无毒药物可接受的盐，其中[E]是雌激素，[DHC]是二氢吡啶盐氧化还原载体的还原、可生物氧化、穿过血脑屏障、脂溶性形式。本发明还公开了用于该主题方法的组合物。一种用于该方法和组合物的优选化合物是雌二醇衍生物，即17.beta.-[(1-甲基-1,4-二氢吡啶基)羰氧基]麦角甾-1,3,5（10）-三烯-3-醇。