(S)-2-((1S,2S,4R,6R)-6-hydroxybicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one | 1334758-47-2

• 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: (S)-2-((1S,2S,4R,6R)-6-hydroxybicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one
• 英文别名: (5S)-2-[[(1S,2S,4R,6R)-6-hydroxy-2-bicyclo[2.2.1]heptanyl]imino]-5-methyl-5-propan-2-yl-1,3-thiazolidin-4-one
• CAS: 1334758-47-2
• 化学式: C₁₄H₂₂N₂O₂S
• 分子量: 282.407
• InChiKey: KIYQVTDQWYFUPA-SLVJWFQDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-((1R,2S,4R)-5-oxobicyclo[2.2.1]hept-5-en-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one 在 硼烷四氢呋喃络合物 、 双氧水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.0h， 生成 2-[[(1S,2S,4R)-6-hydroxy-2-bicyclo[2.2.1]heptanyl]imino]-5-methyl-5-propan-2-yl-1,3-thiazolidin-4-one 、 (S)-2-((1S,2S,4R,6R)-6-hydroxybicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one
  参考文献：
  名称：

  Synthesis and Evaluation of the Metabolites of AMG 221, a Clinical Candidate for the Treatment of Type 2 Diabetes

  摘要：

  All eight of the major active metabolites of (S)-2-(1S,2S,4R)-bicyclo [2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221, compound 1), an inhibitor of 11 beta-hydroxysteroid dehydrogenase type 1 that has entered the clinic for the treatment of type 2 diabetes, were synthetically prepared and confirmed by comparison with samples generated in liver microsomes. After further profiling, we determined that metabolite 2 was equipotent to 1 on human 11 beta-HSD1 and had lower in vivo clearance and higher bioavailability in rat and mouse. Compound 2 was advanced into a pharmacodynamic model in mouse where it inhibited adipose 11 beta-HSD1 activity.

  DOI：

  10.1021/ml2001467

文献信息

• Synthesis and Evaluation of the Metabolites of AMG 221, a Clinical Candidate for the Treatment of Type 2 Diabetes
  作者：Aiwen Li、Chester C. Yuan、David Chow、Michelle Chen、Maurice G. Emery、Clarence Hale、Xiping Zhang、Raju Subramanian、David J. St. Jean、Renee Komorowski、Murielle Véniant、Minghan Wang、Christopher Fotsch

  DOI：10.1021/ml2001467

  日期：2011.11.10

  All eight of the major active metabolites of (S)-2-(1S,2S,4R)-bicyclo [2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221, compound 1), an inhibitor of 11 beta-hydroxysteroid dehydrogenase type 1 that has entered the clinic for the treatment of type 2 diabetes, were synthetically prepared and confirmed by comparison with samples generated in liver microsomes. After further profiling, we determined that metabolite 2 was equipotent to 1 on human 11 beta-HSD1 and had lower in vivo clearance and higher bioavailability in rat and mouse. Compound 2 was advanced into a pharmacodynamic model in mouse where it inhibited adipose 11 beta-HSD1 activity.