2-(4-{2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-4-oxo-4,5-dihydrothiazol-5-yl}phenyl)acetonitrile | 938454-98-9

• 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-(4-{2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-4-oxo-4,5-dihydrothiazol-5-yl}phenyl)acetonitrile
• 英文别名: 2-[4-[2-[(1S)-1-(4-fluorophenyl)ethyl]imino-5-methyl-4-oxo-1,3-thiazolidin-5-yl]phenyl]acetonitrile
• CAS: 938454-98-9
• 化学式: C₂₀H₁₈FN₃OS
• 分子量: 367.447
• InChiKey: LUMLHZQYNSDPKW-SZQRVLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-{2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-4-oxo-4,5-dihydrothiazol-5-yl}phenyl)acetonitrile 在 氢氧化钾 作用下， 以 叔丁醇 为溶剂， 以17%的产率得到2-(4-{2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-4-oxo-4,5-dihydrothiazol-5-yl}phenyl)acetamide
  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：

  5-[4-(chloromethyl)phenyl]-2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methylthiazol-4(5H)-one 、 氰化四丁基铵 以 二氯甲烷 为溶剂， 以63%的产率得到2-(4-{2-[(S)-1-(4-fluorophenyl)ethylamino]-5-methyl-4-oxo-4,5-dihydrothiazol-5-yl}phenyl)acetonitrile
  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

• 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。
• US8541592B2
  申请人：——

  公开号：US8541592B2

  公开（公告）日：2013-09-24
• [EN] INHIBITORS OF 11-BETA-HYDROXY STEROID DEHYDROGENASE TYPE 1<br/>[FR] INHIBITEURS DE LA 11-BETA-HYDROXY STEROIDE DESHYDROGENASE DE TYPE 1
  申请人：AMGEN INC

  公开号：WO2007061661A2

  公开（公告）日：2007-05-31

  (EN) 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-&bgr;-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11- &bgr;-hydroxysteroid dehydrogenase type 1 enzyme.(FR) La présente invention concerne des thiazolinones et des compositions pharmaceutiques comprenant ces composés, ainsi que des procédés d’utilisation de ces composés pour le traitement des pathologies associées à l’enzyme humaine 11-&bgr;-hydroxystéroide déshydrogénase de type 1 et pour la préparation d’un médicament agissant sur cette enzyme.