(+/-)-exo-1-(bicyclo[2.2.1]heptan-2-yl)thiourea | 65069-57-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+/-)-exo-1-(bicyclo[2.2.1]heptan-2-yl)thiourea
• 英文别名: rel-N-(1R,2R,4S)-Bicyclo[2.2.1]hept-2-ylthiourea；[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]thiourea
• CAS: 65069-57-0
• 化学式: C₈H₁₄N₂S
• 分子量: 170.279
• InChiKey: HXTOTKHBSWGCMX-RRKCRQDMSA-N

物化性质

• 沸点：
  281.3±23.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.01
• 重原子数：
  11.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  38.05
• 氢给体数：
  2.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  (+/-)-exo-1-(bicyclo[2.2.1]heptan-2-yl)thiourea 以 丙酮 、 叔丁醇 为溶剂， 反应 21.0h， 生成 (1S,2S,4R)-N-Bicyclo[2.2.1]hept-2-yl-morpholine-4-carboxamidine; hydriodide
  参考文献：
  名称：

  A Versatile Synthesis of NovelN,N,N″-Trisubstituted Guanidines

  摘要：

  N,N,N″-三取代胍（大部分是N″-芳基-N-氮杂环烷羧基亚胺）通常以良好的产率通过以下步骤制备：将单取代硫脲与甲基碘在甲醇或丙酮中进行S-甲基化反应，然后将所得的甲基氨基甲亚胺硫醇氢碘酸盐与二级胺在沸腾的叔丁醇或丙酮腈中反应。

  DOI：

  10.1055/s-1988-27606
• 作为产物：
  描述：

  exo-Bicyclo<2.2.1>heptan-2-yl isothiocyanate 在 氨 作用下， 以 乙二醇二甲醚 为溶剂， 以88%的产率得到(+/-)-exo-1-(bicyclo[2.2.1]heptan-2-yl)thiourea
  参考文献：
  名称：

  Improved Procedures for the Preparation of Cycloalkyl-, Arylalkyl-, and Arylthioureas

  摘要：

  制备芳基硫脲的改进方法包括将苯甲酰异硫氰酸酯与苯胺在丙酮中反应，然后用5%氢氧化钠水溶液对生成的N-芳基-N'-苯甲酰硫脲进行去苯甲酰化。双环烷基硫脲和N-(芳烷基)硫脲（例如9H-9-芴基硫脲）可直接由相应的异硫氰酸酯与氨反应制备。

  DOI：

  10.1055/s-1988-27605

文献信息

• [EN] INHIBITORS OF 11-BETA-HYDROXY STEROID DEHYDROGENASE TYPE 1<br/>[FR] INHIBITEURS DE LA 11-BETA-HYDROXY STEROIDE DESHYDROGENASE DE TYPE 1
  申请人：AMGEN INC

  公开号：WO2007061661A4

  公开（公告）日：2009-01-29
• Comparison of Large-Scale Routes to Manufacture Chiral <i>exo</i>-2-Norbornyl Thiourea
  作者：Seb Caille、Jerome Boni、Geoffrey B. Cox、Margaret M. Faul、Pilar Franco、Saab Khattabi、Liane M. Klingensmith、Jay F. Larrow、James K. Lee、Michael J. Martinelli、Larry M. Miller、George A. Moniz、Kenichi Sakai、Jason S. Tedrow、Karl B. Hansen

  DOI：10.1021/op9002328

  日期：2010.1.15

  Two routes aimed at the manufacture of chiral exo-2-norbornyl thiourea (1) on large scale are described. The first approach involves live chemical steps and hinges on a classical resolution via diastereomeric salt formation. The synthesis utilizes amine 2 as the resolution handle. The second approach includes two chemical steps and a chiral chromatography of (+/-)-1. Despite the larger initial investment necessary to acquire the chiral stationary phase used in the chromatographic approach, the shorter reaction sequence and efficiency of the chromatographic separation make the second route a more attractive option tor long-term applications.
• Discovery of a Potent, Orally Active 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor for Clinical Study: Identification of (<i>S</i>)-2-((1<i>S</i>,2<i>S</i>,4<i>R</i>)-Bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5<i>H</i>)-one (AMG 221)
  作者：Murielle M. Véniant、Clarence Hale、Randall W. Hungate、Kyung Gahm、Maurice G. Emery、Janan Jona、Smriti Joseph、Jeffrey Adams、Andrew Hague、George Moniz、Jiandong Zhang、Michael D. Bartberger、Vivian Li、Rashid Syed、Steven Jordan、Renée Komorowski、Michelle M. Chen、Rod Cupples、Ki Won Kim、David J. St. Jean、Lars Johansson、Martin A. Henriksson、Meredith Williams、Jerk Vallgårda、Christopher Fotsch、Minghan Wang

  DOI：10.1021/jm100242d

  日期：2010.6.10

  Thiazolones with an exo-norbornylamine at the 2-position and an isopropyl group on the 5-position are potent 11 beta-HSD1 inhibitors. However, the C-5 center was prone to epimerization in vitro and in vivo, forming a less potent diastereomer. A methyl group was added to the C-5 position to eliminate epimerization, leading to the discovery of (S)-2-(1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). This compound decreased fed blood glucose and insulin levels and reduced body weight in diet-induced obesity mice.