(1R,5S)-8-苄基-8-氮杂双环[3.2.1]辛烷-2-酮 | 208037-76-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (1R,5S)-8-苄基-8-氮杂双环[3.2.1]辛烷-2-酮
• 英文名称: (1R,5S)-8-benzyl-8-azabicyclo[3.2.1]octan-2-one
• 英文别名: 8-benzyl-8-azabicyclo[3.2.1]octan-2-one
• CAS: 208037-76-7
• 化学式: C₁₄H₁₇NO
• 分子量: 215.295
• InChiKey: GWVYHAOGBUOWIL-QWHCGFSZSA-N

物化性质

• 沸点：
  330.5±25.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,5S)-8-苄基-8-氮杂双环[3.2.1]辛烷-2-酮 在 palladium on activated charcoal 4-二甲氨基吡啶 、 sodium hydroxide 、 氢气 、 双氧水 、 sodium hydride 、 sodium cyanoborohydride 、 sodium carbonate 、 三氟乙酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸酐 、 溶剂黄146 、 甲苯 、 乙腈 为溶剂， 反应 93.67h， 生成 古卡因
  参考文献：
  名称：

  Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid

  摘要：

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.

  DOI：

  10.1021/jo980153t
• 作为产物：
  描述：

  3-((2R,5S)-1-benzyl-5-(tert-butoxycarbonyl)pyrrolidin-2-yl)propanoic acid 在 吡啶 、 乙酰氯 、 sodium iodide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 13.75h， 生成 (1R,5S)-8-苄基-8-氮杂双环[3.2.1]辛烷-2-酮
  参考文献：
  名称：

  [EN] DIAMINOCYCLOHEXANE COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS DE DIAMINOCYCLOHEXANE ET LEURS UTILISATIONS

  摘要：

  本发明提供了化合物的结构式（I），或其立体异构体，或其药学上可接受的盐，其中所有变量均如本文所定义。这些化合物是NPY Y4受体的激动剂、部分激动剂和调节剂，可用于治疗和预防各种疾病和病况。

  公开号：

  WO2013012827A1

文献信息

• Pyrimidoaminotropanes as Potent, Selective, and Efficacious Small Molecule Kinase Inhibitors of the Mammalian Target of Rapamycin (mTOR)
  作者：Anthony A. Estrada、Daniel G. Shore、Elizabeth Blackwood、Yung-Hsiang Chen、Gauri Deshmukh、Xiao Ding、Antonio G. DiPasquale、Jennifer A. Epler、Lori S. Friedman、Michael F. T. Koehler、Lichuan Liu、Shiva Malek、Jim Nonomiya、Daniel F. Ortwine、Zhonghua Pei、Steve Sideris、Frederic St-Jean、Lan Trinh、Tom Truong、Joseph P. Lyssikatos

  DOI：10.1021/jm400194n

  日期：2013.4.11

  We have recently reported a series of tetrahydroquinazoline (THQ) mTOR inhibitors that produced a clinical candidate 1 (GDC-0349). Through insightful design, we hoped to discover and synthesize a new series of small molecule inhibitors that could attenuate CYP3A4 time-dependent inhibition commonly observed with the THQ scaffold, maintain or improve aqueous solubility and oral absorption, reduce free drug clearance, and selectively increase mTOR potency. Through key in vitro and in vivo studies, we demonstrate that a pyrimidoaminotropane based core was able to address each of these goals. This effort culminated in the discovery of 20 (GNE-555), a highly potent, selective, metabolically stable, and efficacious mTOR inhibitor.