N-(1-norbornyl)thiourea | 870708-36-4

• 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: N-(1-norbornyl)thiourea
• 英文别名: 1-(Bicyclo[2.2.1]heptan-1-yl)thiourea；1-bicyclo[2.2.1]heptanylthiourea
• CAS: 870708-36-4
• 化学式: C₈H₁₄N₂S
• 分子量: 170.279
• InChiKey: NYKABPMOBIJFCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  70.1
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-溴-2-甲基丁酸甲酯 、 N-(1-norbornyl)thiourea 以 1,4-二氧六环 为溶剂， 反应 96.0h， 以38%的产率得到5-ethyl-5-methyl-2-(1-norbornylamino)-1,3-thiazol-4(5H)-one
  参考文献：
  名称：

  2-Amino-1,3-thiazol-4(5H)-ones as Potent and Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors: Enzyme−Ligand Co-Crystal Structure and Demonstration of Pharmacodynamic Effects in C57Bl/6 Mice

  摘要：

  11 beta-Hydroxy steroid dehydrogenase type 1 (11 beta-HSD1) has attracted considerable attention during the past few years as a potential target for the treatment of diseases associated with metabolic syndrome. In our ongoing work on 11-HSD1 inhibitors, a series of new 2-amino-1,3-thiazol-4(5H)-ones were explored. By inserting various cycloalkylamines at the 2-position and alkyl groups or spirocycloalkyl groups at the 5-position of the thiazolone, several potent 11 beta-HSD1 inhibitors were identified. An X-ray cocrystal structure of human 11 beta-HSD1 with compound 6d (K-i = 28 nM) revealed a large lipophilic pocket accessible by substitution off the 2-position of the thiazolone. To increase potency, analogues were prepared with larger lipophilic groups at this position. One of these compounds, the 3-noradamantyl analogue 8b, was a potent inhibitor of human 11 beta-HSD 1 (K-i = 3 nM) and also inhibited 11 beta-HSD1 activity in lean C57BI/6 mice when evaluated in an ex vivo adipose and liver cortisone to cortisol conversion assay.

  DOI：

  10.1021/jm701551j
• 作为产物：
  描述：

  双环[2.2.1]庚烷-1-胺 、 异硫氰酰甲酸乙酯 在 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 5.58h， 以139 mg的产率得到N-(1-norbornyl)thiourea
  参考文献：
  名称：

  2-Amino-1,3-thiazol-4(5H)-ones as Potent and Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors: Enzyme−Ligand Co-Crystal Structure and Demonstration of Pharmacodynamic Effects in C57Bl/6 Mice

  摘要：

  11 beta-Hydroxy steroid dehydrogenase type 1 (11 beta-HSD1) has attracted considerable attention during the past few years as a potential target for the treatment of diseases associated with metabolic syndrome. In our ongoing work on 11-HSD1 inhibitors, a series of new 2-amino-1,3-thiazol-4(5H)-ones were explored. By inserting various cycloalkylamines at the 2-position and alkyl groups or spirocycloalkyl groups at the 5-position of the thiazolone, several potent 11 beta-HSD1 inhibitors were identified. An X-ray cocrystal structure of human 11 beta-HSD1 with compound 6d (K-i = 28 nM) revealed a large lipophilic pocket accessible by substitution off the 2-position of the thiazolone. To increase potency, analogues were prepared with larger lipophilic groups at this position. One of these compounds, the 3-noradamantyl analogue 8b, was a potent inhibitor of human 11 beta-HSD 1 (K-i = 3 nM) and also inhibited 11 beta-HSD1 activity in lean C57BI/6 mice when evaluated in an ex vivo adipose and liver cortisone to cortisol conversion assay.

  DOI：

  10.1021/jm701551j

文献信息

• [EN] ASYMMETRIC PROCESS FOR MAKING SUBSTITUTED 2-AMINO-THIAZOLONES<br/>[FR] PROCESSUS ASYMÉTRIQUE POUR LA FABRICATION DE 2-AMINO-THIAZOLONES
  申请人：AMGEN INC

  公开号：WO2010014586A1

  公开（公告）日：2010-02-04

  The invention provides two process for synthesizing substituted aminothiazolone compounds as inhibitors of 11-β-hydroxy steroid dehydrogenase type 1. The processes allow the stereoselective synthesis of the desired compounds without the use of stoichiometric amounts of chiral catalysts.

  这项发明提供了两种合成取代氨基噻唑酮化合物的方法，作为11-β-羟基类固醇脱氢酶1的抑制剂。这些方法允许在不使用化学计量的手性催化剂的情况下，对所需化合物进行立体选择性合成。
• Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1
  申请人：Henriksson Martin

  公开号：US20060142357A1

  公开（公告）日：2006-06-29

  The present invention relates to compounds with the formula (I), (II), (III) or (IV): wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X and Z are as defined herein, 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.

  本发明涉及具有式（I），（II），（III）或（IV）的化合物：其中R1，R2，R3，R4，R5，R6，R7，X和Z如本文所定义，并且还涉及包含该化合物的制药组合物，以及使用该化合物治疗与人类11-β-羟基类固醇脱氢酶1型酶相关的疾病和制备作用于人类11-β-羟基类固醇脱氢酶1型酶的药物的方法。
• Inhibitors of 11-β-hydroxy steroid dehydrogenase type 1
  申请人：Amgen, Inc.

  公开号：US07253196B2

  公开（公告）日：2007-08-07

  The present invention relates to compounds with the formula (I), (II), (III) or (IV): wherein R1, R2, R3, R4, R5, R6, R7, X and Z are as defined herein, 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.

  本发明涉及公式（I），（II），（III）或（IV）的化合物： 其中R1，R2，R3，R4，R5，R6，R7，X和Z如定义所述，并且还涉及包含该化合物的制药组合物，以及使用该化合物治疗与人类11-β-羟基类固醇脱氢酶类型1酶相关的疾病的方法，以及用于制备作用于人类11-β-羟基类固醇脱氢酶类型1酶的药物。
• Inhibitors of 11-Beta-Hydroxy Steroid Dehydrogenase Type 1
  申请人：Henriksson Martin

  公开号：US20070281938A1

  公开（公告）日：2007-12-06

  The present invention relates to compounds with the formula (I) wherein R 1 , R 2 , R 3 , R 4 , and Z are as defined herein, and also to pharmaceutical compositions comprising the compounds, as well as to the use of the compounds in medicine and for the preparation of a medicament which acts on the human 11-β-hydroxysteroid dehydrogenase type 1 enzyme.

  本发明涉及化合物式（I），其中R1、R2、R3、R4和Z的定义如本文所述，以及包含该化合物的制药组合物，以及该化合物在医学上的使用和用于制备对人类11-β-羟基类固醇脱氢酶1型酶起作用的药物。
• ASYMMETRIC PROCESS FOR MAKING SUBSTITUTED 2-AMINO-THIAZOLONES
  申请人：Caille Seb

  公开号：US20110178307A1

  公开（公告）日：2011-07-21

  The invention provides two process for synthesizing substituted aminothiazolone compounds as inhibitors of 11-β-hydroxy steroid dehydrogenase type 1. The processes allow the stereoselective synthesis of the desired compounds without the use of stoichiometric amounts of chiral catalysts.

  本发明提供了两种合成取代氨基噻唑酮化合物作为11-β-羟基类固醇脱氢酶1型抑制剂的方法。这些方法允许对所需化合物进行立体选择性合成，而无需使用化学手性催化剂的化学计量量。