(2S)-2-[[(3β,15α,16α,23R,24S)-16,23-epoxy-24-ethoxy-15,25-dihydroxy-9,19-cyclolanostan-3-yl]oxy]-4-(1-isopropylazetidin-3-yl)morpholine | 1426229-53-9

• 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: (2S)-2-[[(3β,15α,16α,23R,24S)-16,23-epoxy-24-ethoxy-15,25-dihydroxy-9,19-cyclolanostan-3-yl]oxy]-4-(1-isopropylazetidin-3-yl)morpholine
• 英文别名: SPI-1865；(1S,4R,5R,6R,8R,10S,11R,12S,13R,16R,18S,21R)-8-[(1S)-1-ethoxy-2-hydroxy-2-methylpropyl]-4,6,12,17,17-pentamethyl-18-[(2S)-4-(1-propan-2-ylazetidin-3-yl)morpholin-2-yl]oxy-9-oxahexacyclo[11.9.0.01,21.04,12.05,10.016,21]docosan-11-ol
• CAS: 1426229-53-9
• 化学式: C₄₂H₇₂N₂O₆
• 分子量: 701.043
• InChiKey: ITAXZEXGQGVKHD-GYTYNMETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  50
• 可旋转键数：
  8
• 环数：
  8.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  83.9
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [(1S)-2-hydroxy-2-methyl-1-[(1S,4R,5R,6R,8R,10S,12S,13R,16R,18S,21R)-4,6,12,17,17-pentamethyl-11-oxo-18-[(2S)-4-(1-propan-2-ylazetidin-3-yl)morpholin-2-yl]oxy-9-oxahexacyclo[11.9.0.01,21.04,12.05,10.016,21]docosan-8-yl]propyl] acetate 在 sodium tetrahydroborate 、 sodium hydroxide 、 sodium t-butanolate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 79.0h， 生成 (2S)-2-[[(3β,15α,16α,23R,24S)-16,23-epoxy-24-ethoxy-15,25-dihydroxy-9,19-cyclolanostan-3-yl]oxy]-4-(1-isopropylazetidin-3-yl)morpholine
  参考文献：
  名称：

  公斤级三萜类萜烯衍生的γ-秘密酶调节剂的有效千克级合成的优化。

  摘要：

  这项工作描述了从植物固醇衍生的起始原料公斤级合成γ-分泌酶调节剂的演示。开发能够递送一公斤目标化合物的合成路线的关键是开发四反应望远镜工艺和三醇中间体的选择性O-烷基化。这些改进使得能够成功交付千克级的API，用于临床前开发研究。

  DOI：

  10.1021/op500072b

文献信息

• [EN] COMPOUNDS USEFUL FOR TREATING NEURODEGENERATIVE DISORDERS<br/>[FR] COMPOSÉS UTILES POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：SATORI PHARMACEUTICALS INC

  公开号：WO2013036669A1

  公开（公告）日：2013-03-14

  The present invention provides compounds useful for treating or lessening the severity of a neurodegenerative disorder. The present invention also provides methods of treating or lessening the severity of such disorders wherein said method comprises administering to a patient a compound of the present invention, or composition thereof. Said method is useful for treating or lessening the severity of, for example, Alzheimer's disease.

  本发明提供了用于治疗或减轻神经退行性疾病严重程度的化合物。本发明还提供了治疗或减轻这类疾病严重程度的方法，其中该方法包括向患者施用本发明的化合物或其组合物。该方法适用于治疗或减轻例如阿尔茨海默病等疾病的严重程度。
• [EN] COMPOUNDS FOR USE IN TREATING NEURODEGENERATIVE DISORDERS, SYNTHESIS THEREOF, AND INTERMEDIATES THERETO<br/>[FR] COMPOSÉS UTILES POUR LE TRAITEMENT DE MALADIES DÉGÉNÉRATIVES, SYNTHÈSE DE CES COMPOSÉS ET LEURS INTERMÉDIAIRES
  申请人：SATORI PHARMACEUTICALS INC

  公开号：WO2013036665A1

  公开（公告）日：2013-03-14

  The present invention provides methods for preparing compounds useful as modulators of amyloid-beta production. Such compounds are useful for treating or lessening the severity of a neurodegenerative disorder. The present invention also provides intermediates useful in carrying out such synthetic methods. Compounds of this invention are further illustrated by the embodiments, sub-embodiments, and species disclosed herein.

  本发明提供了用作淀粉样蛋白β产生调节剂的化合物制备方法。这些化合物可用于治疗或减轻神经退行性疾病的严重程度。本发明还提供了在执行这些合成方法中有用的中间体。本发明的化合物通过本文所披露的实施方式、子实施方式和种属进一步加以说明。
• Compounds useful for treating neurodegenerative disorders
  申请人：Bronk Brian Scott

  公开号：US20130060020A1

  公开（公告）日：2013-03-07

  The present invention provides compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein R x is as defined and described herein, compositions thereof, and methods of using the same.

  本发明提供了公式I的化合物：或其药学上可接受的盐，其中Rxis的定义和描述如本文所述，以及其组合物和使用方法。
• Compounds for Use in Treating Neurodegenerative Disorders, Synthesis Thereof, and Intermediates Thereto
  申请人：Bronk Brian Scott

  公开号：US20130060019A1

  公开（公告）日：2013-03-07

  The present invention provides methods of making a compound of formula II: or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , and L are as defined and described herein.

  本发明提供了制备II式化合物的方法，或其药学上可接受的盐，其中R1，R2和L如本文所定义和描述。
• Minimization of drug–drug interaction risk and candidate selection in a natural product-based class of gamma-secretase modulators
  作者：Jed L. Hubbs、Nathan O. Fuller、Wesley F. Austin、Ruichao Shen、Jianguo Ma、Zhen Gong、Jian Li、Timothy D. McKee、Robyn M.B. Loureiro、Barbara Tate、Jo Ann Dumin、Jeffrey Ives、Brian S. Bronk

  DOI：10.1016/j.bmcl.2015.01.051

  日期：2015.4

  Early lead compounds in this gamma secretase modulator series were found to potently inhibit CYP3A4 and other human CYP isoforms increasing their risk of causing drug-drug-interactions (DDIs). Using structure-activity relationships and CYP3A4 structural information, analogs were developed that minimized this DDI potential. Three of these new analogs were further characterized by rat PK, rat PK/PD and rat exploratory toxicity studies resulting in selection of SPI-1865 (14) as a preclinical development candidate. (C) 2015 Elsevier Ltd. All rights reserved.