1-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-yl)thiourea | 1191465-55-0

• 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: 1-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-yl)thiourea
• 英文别名: [(1R,2S,4R,5S)-5-[tert-butyl(diphenyl)silyl]oxy-2-bicyclo[2.2.1]heptanyl]thiourea
• CAS: 1191465-55-0
• 化学式: C₂₄H₃₂N₂OSSi
• 分子量: 424.682
• InChiKey: STWNNFVBYAGFCI-UBBRYJJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  79.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-yl)thiourea 在 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 hexanes 、 乙醇 为溶剂， 反应 5.0h， 生成 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 、 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 78.0h， 生成 1-((1R,2S,4R,5S)-5-(tert-butyldiphenylsilyloxy)bicyclo[2.2.1]heptan-2-yl)thiourea
  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

• Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
  申请人：Henriksson Martin

  公开号：US20070197598A1

  公开（公告）日：2007-08-23

  The present invention relates to thiazolinones and also to pharmaceutical compositions comprising the compounds, as well as methods of use of the compounds for treatment of disorders associated with human 11-β-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11-β-hydroxysteroid dehydrogenase type 1 enzyme.

  本发明涉及噻唑酮，以及包含该化合物的药物组合物，以及使用该化合物治疗与人类11-β-羟基类固醇脱氢酶1型酶相关的疾病的方法，以及用于制备作用于人类11-β-羟基类固醇脱氢酶1型酶的药物的方法。
• Inhibitors of 11-beta-hydroxysteroid dehydrogenase type 1
  申请人：Henriksson Martin

  公开号：US08541592B2

  公开（公告）日：2013-09-24

  The present invention relates to thiazolinones and also to pharmaceutical compositions comprising the compounds, as well as methods of use of the compounds for treatment of disorders associated with human 11-β-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11-β-hydroxysteroid dehydrogenase type 1 enzyme.

  本发明涉及噻唑烷酮，以及包含该化合物的药物组合物，以及使用该化合物治疗与人类11-β-羟基类固醇脱氢酶1型酶相关的疾病的方法，以及制备对人类11-β-羟基类固醇脱氢酶1型酶起作用的药物的方法。
• 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.