2-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-ylamino)-5-isopropylthiazol-4(5H)-one | 1334758-82-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-ylamino)-5-isopropylthiazol-4(5H)-one
• CAS: 1334758-82-5
• 化学式: C₂₉H₃₈N₂O₂SSi
• 分子量: 506.784
• InChiKey: CCPXDXGSSRAYNW-NLXXYILZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.97
• 重原子数：
  35.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  50.69
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)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 、 hexanes 为溶剂， 反应 4.0h， 以74%的产率得到2-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)bicyclo[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
• 作为产物：
  描述：

  (rac)-(exo,exo)-bicyclo[2.2.1]heptane-2,5-diol 在 咪唑 、 15-冠醚-5 、 palladium 10% on activated carbon 、 氢气 、 L-Selectride 、 N,N-二异丙基乙胺 、 三苯基膦 、 pyridinium chlorochromate 、 sodium hydroxide 、 肼 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 79.0h， 生成 2-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-ylamino)-5-isopropylthiazol-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