2-[(S)-1-(2-chlorophenyl)ethylamino]-5-methylthiazol-4(5H)-one | 937187-44-5

• 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-[(S)-1-(2-chlorophenyl)ethylamino]-5-methylthiazol-4(5H)-one
• 英文别名: 5-methyl-2-((S)-1-(2-chlorophenyl)ethylamino)thiazol-4(5H)-one；2-[(1S)-1-(2-chlorophenyl)ethyl]imino-5-methyl-1,3-thiazolidin-4-one
• CAS: 937187-44-5
• 化学式: C₁₂H₁₃ClN₂OS
• 分子量: 268.767
• InChiKey: VXXLDYWNCUZHMU-JAMMHHFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 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：
  3

反应信息

• 作为反应物：
  描述：

  2-[(S)-1-(2-chlorophenyl)ethylamino]-5-methylthiazol-4(5H)-one 、 丙酮 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以76%的产率得到2-[(S)-1-(2-chlorophenyl)ethylamino]-5-(2-hydroxypropan-2-yl)-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。
• 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。
• CATALYZED PROCESS OF MAKING C-5-SUBSTITUTED HETEROCYCLIC INHIBITORS OF 11ß-HYDROXY STEROID DEHYDROGENASE TYPE 1
  申请人：Amgen Inc.

  公开号：EP1951695A1

  公开（公告）日：2008-08-06
• US7541474B2
  申请人：——

  公开号：US7541474B2

  公开（公告）日：2009-06-02
• [EN] CATALYZED PROCESS OF MAKING C-5-SUBSTITUTED HETEROCYCLIC INHIBITORS OF 11ß-HYDROXY STEROID DEHYDROGENASE TYPE 1<br/>[FR] PROCÉDÉ CATALYTIQUE DE SYNTHÈSE D'INHIBITEURS HÉTÉROCYCLIQUES C-5-SUBSTITUÉS DE LA 11ß-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1
  申请人：AMGEN INC

  公开号：WO2007061600A1

  公开（公告）日：2007-05-31

  [EN] The invention provides a process for preparing 11 ß-hydroxy steroid dehydrogenase type 1 inhibitors of formula (II) via a catalyzed reaction between a compound of formula (I) 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.
  [FR] La présente invention concerne un procédé de synthèse d'inhibiteurs de la 11ß-hydroxystéroïde déshydrogénase de type 1 de formule 2 par une réaction catalytique entre un composé de formule 1 et un composé de formule R²LG en présence d'une base : où R¹, R², X, Y et LG sont définis dans la description. Les catalyseurs exemplifiant l'invention contiennent du palladium et un ou plusieurs ligands phosphine. Le procédé peut être mené de façon stéréosélective pour aboutir à des produits énantiomériquement enrichis.