2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methylthiazol-4(5H)-one | 870709-87-8

• 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-[(S)-1-(4-fluorophenyl)ethylamino]-5-methylthiazol-4(5H)-one
• 英文别名: 5-methyl-2-((S)-1-(4-fluorophenyl)ethylamino)thiazol-4(5H)-one；2-[(1S)-1-(4-fluorophenyl)ethyl]imino-5-methyl-1,3-thiazolidin-4-one
• CAS: 870709-87-8
• 化学式: C₁₂H₁₃FN₂OS
• 分子量: 252.312
• InChiKey: GOOACXKEDTUBGL-JAMMHHFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methylthiazol-4(5H)-one 、 methyloxirane 在 lithium hexamethyldisilazane 、 lithium perchlorate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以71%的产率得到2-[(S)-1-(4-fluorophenyl)ethylamino]-5-(2-hydroxypropyl)-5-methylthiazol-4(5H)-one
  参考文献：
  名称：

  Further Studies with the 2-Amino-1,3-thiazol-4(5H)-one Class of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors: Reducing Pregnane X Receptor Activity and Exploring Activity in a Monkey Pharmacodynamic Model

  摘要：

  A series of compounds containing the 2-amino-1,3-thiazol-4(5H)-one core were found to be potent inhibitors of the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). One of our lead compounds from this series activated the human nuclear xenobiotic receptor, pregnane X receptor (PXR). To try and mitigate the PXR activity, we prepared analogues of our lead series that contained polar groups on the right-hand side of the thiazolone. Several analogues containing amides or alcohols appended to the C-5 position of the thiazolone showed a significant reduction in PXR activity. Through these structure-activity efforts, a compound containing a tert-alcohol group off the C-5 position, analogue (S)-33a, Was found to have an 11 beta-HSD1 K(i) = 35 nM and negligible PXR activity. Compound (S)-33a was advanced into a pharmacodynamic model in cynomolgus monkeys, where it inhibited adipose 11 beta-HSD1 activity after being orally administered.

  DOI：

  10.1021/jm801073z
• 作为产物：
  描述：

  (S)-1-[1-(4-fluorophenyl)ethyl]thiourea 、 2-溴丙酸 在 sodium acetate 作用下， 以 乙醇 为溶剂， 以91%的产率得到2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methylthiazol-4(5H)-one
  参考文献：
  名称：

  Further Studies with the 2-Amino-1,3-thiazol-4(5H)-one Class of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors: Reducing Pregnane X Receptor Activity and Exploring Activity in a Monkey Pharmacodynamic Model

  摘要：

  A series of compounds containing the 2-amino-1,3-thiazol-4(5H)-one core were found to be potent inhibitors of the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). One of our lead compounds from this series activated the human nuclear xenobiotic receptor, pregnane X receptor (PXR). To try and mitigate the PXR activity, we prepared analogues of our lead series that contained polar groups on the right-hand side of the thiazolone. Several analogues containing amides or alcohols appended to the C-5 position of the thiazolone showed a significant reduction in PXR activity. Through these structure-activity efforts, a compound containing a tert-alcohol group off the C-5 position, analogue (S)-33a, Was found to have an 11 beta-HSD1 K(i) = 35 nM and negligible PXR activity. Compound (S)-33a was advanced into a pharmacodynamic model in cynomolgus monkeys, where it inhibited adipose 11 beta-HSD1 activity after being orally administered.

  DOI：

  10.1021/jm801073z

文献信息

• Catalyzed process of making C-5-substituted heterocyclic inhibitors of 11beta-hydroxy steroid dehydrogenase type 1
  申请人：Bunel Emilio

  公开号：US20070117985A1

  公开（公告）日：2007-05-24

  The invention provides a process for preparing 11 β-hydroxy steroid dehydrogenase type 1 inhibitors of formula 2 via a catalyzed reaction between a compound of formula 1 and a compound of formula R 2 LG in the presence of base: where R 1 , R 2 , X, Y, and LG are described in the specification. Exemplary catalysts contain palladium and one or more phosphine ligands. The process can be performed in a stereoselective manner to give enantiomerically enriched products.

  本发明提供了一种制备11β-羟基类固醇脱氢酶1型抑制剂2的方法，该方法通过在碱存在下，化合物1和化合物R2LG之间催化反应而得到。其中，R1、R2、X、Y和LG在说明书中有描述。示例催化剂包含钯和一个或多个膦配体。该过程可以立体选择性地进行，以得到对映体富集的产物。
• 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-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。
• Catalyzed process of making C-5-substituted heterocyclic inhibitors of 11β-hydroxy steroid dehydrogenase type 1
  申请人：Amgen Inc.

  公开号：US07541474B2

  公开（公告）日：2009-06-02

  The invention provides a process for preparing 11 β-hydroxy steroid dehydrogenase type 1 inhibitors of formula 2 via a catalyzed reaction between a compound of formula 1 and a compound of formula R2LG in the presence of base: where R1, R2, X, Y, and LG are described in the specification. Exemplary catalysts contain palladium and one or more phosphine ligands. The process can be performed in a stereoselective manner to give enantiomerically enriched products.

  该发明提供了一种制备11β-羟基类固醇脱氢酶1型抑制剂的方法，该方法通过在碱存在下，化合物1和化合物R2LG之间的催化反应制备公式2的产物，其中R1、R2、X、Y和LG在说明书中描述。示例催化剂包含钯和一个或多个膦配体。该过程可以立体选择性地进行，以给出对映体富集的产物。
• INHIBITORS OF 11-BETA-HYDROXY STEROID DEHYDROGENASE TYPE 1
  申请人：Henriksson Martin

  公开号：US20110082107A1

  公开（公告）日：2011-04-07

  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，并且还涉及包含这些化合物的制药组合物，以及使用这些化合物治疗与人类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。