2-(endo-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropylthiazol-4(5H)-one | 1228462-66-5

• 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: 2-(endo-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropylthiazol-4(5H)-one
• 英文别名: 2-[[(1R,2R,4S)-2-bicyclo[2.2.1]heptanyl]imino]-5-propan-2-yl-1,3-thiazolidin-4-one
• CAS: 1228462-66-5
• 化学式: C₁₃H₂₀N₂OS
• 分子量: 252.381
• InChiKey: HSBAWYZAAMESPW-JSBCTHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(endo-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropylthiazol-4(5H)-one 、 碘甲烷 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-2-((1R,2R,4S)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one 、 (R)-2-((1R,2R,4S)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one
  参考文献：
  名称：

  Discovery of a Potent, Orally Active 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor for Clinical Study: Identification of (S)-2-((1S,2S,4R)-Bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221)

  摘要：

  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.

  DOI：

  10.1021/jm100242d

文献信息

• 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.