2-((S)-1-(2-fluorophenyl)ethylamino)-5-(2-hydroxypropan-2-yl)-5-methylthiazol-4(5H)-one | 870713-26-1

• 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-fluorophenyl)ethylamino)-5-(2-hydroxypropan-2-yl)-5-methylthiazol-4(5H)-one
• 英文别名: 2-[(S)-1-(2-fluorophenyl)ethylamino]-5-(2-hydroxypropan-2-yl)-5-methylthiazol-4(5H)-one；2-[(S)-1-(2-Fluorophenyl)ethylamino]-5-(2-hydroxypropan-2-yl)-5-methylthiazol-4(5H)-one；2-[(1S)-1-(2-fluorophenyl)ethyl]imino-5-(2-hydroxypropan-2-yl)-5-methyl-1,3-thiazolidin-4-one
• CAS: 870713-26-1
• 化学式: C₁₅H₁₉FN₂O₂S
• 分子量: 310.392
• InChiKey: ZSRUMWXDCGNNPN-HJULIUOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((S)-1-(2-fluorophenyl)ethylamino)-5-(2-hydroxypropan-2-yl)-5-methylthiazol-4(5H)-one 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 以52%的产率得到2-{[(1S)-1-(2-fluorophenyl)ethyl]amino}-5-(2-fluoropropan-2-yl)-5-methyl-4,5-dihydro-1,3-thiazol-4-one
  参考文献：
  名称：

  2-(S)-Phenethylaminothiazolones as Potent, Orally Efficacious Inhibitors of 11β-Hydroxysteriod Dehydrogenase Type 1

  摘要：

  11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is the enzyme that converts cortisone to cortisol. A growing body of evidence suggests that selective inhibition of 11 beta-HSD1 could potentially treat metabolic syndrome as well as type 2 diabetes. Through modification of our initial lead 1, we have discovered trifluoromethyl thiazolone 17. This compound had a K-i of 22 nM, possessed low in vivo clearance, and showed a 91% inhibition of adipose 11 beta-HSD1 enzymatic activity in a mouse ex vivo pharmacodynamic model.

  DOI：

  10.1021/jm061214f
• 作为产物：
  描述：

  在 氢氧化钾 、 sodium acetate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正庚烷 、 乙基苯 为溶剂， 反应 3.58h， 生成 2-((S)-1-(2-fluorophenyl)ethylamino)-5-(2-hydroxypropan-2-yl)-5-methylthiazol-4(5H)-one
  参考文献：
  名称：

  2-(S)-Phenethylaminothiazolones as Potent, Orally Efficacious Inhibitors of 11β-Hydroxysteriod Dehydrogenase Type 1

  摘要：

  11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is the enzyme that converts cortisone to cortisol. A growing body of evidence suggests that selective inhibition of 11 beta-HSD1 could potentially treat metabolic syndrome as well as type 2 diabetes. Through modification of our initial lead 1, we have discovered trifluoromethyl thiazolone 17. This compound had a K-i of 22 nM, possessed low in vivo clearance, and showed a 91% inhibition of adipose 11 beta-HSD1 enzymatic activity in a mouse ex vivo pharmacodynamic model.

  DOI：

  10.1021/jm061214f

文献信息

• 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。
• 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。
• Further Studies with the 2-Amino-1,3-thiazol-4(5<i>H</i>)-one Class of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors: Reducing Pregnane X Receptor Activity and Exploring Activity in a Monkey Pharmacodynamic Model
  作者：Christopher Fotsch、Michael D. Bartberger、Eric A. Bercot、Michelle Chen、Rod Cupples、Maury Emery、Jenne Fretland、Anil Guram、Clarence Hale、Nianhe Han、Dean Hickman、Randall W. Hungate、Michael Hayashi、Renee Komorowski、Qingyian Liu、Guy Matsumoto、David J. St. Jean、Stefania Ursu、Murielle Véniant、Guifen Xu、Qiuping Ye、Chester Yuan、Jiandong Zhang、Xiping Zhang、Hua Tu、Minghan Wang

  DOI：10.1021/jm801073z

  日期：2008.12.25

  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.
• US7253196B2
  申请人：——

  公开号：US7253196B2

  公开（公告）日：2007-08-07