ethyl 2-(6-fluoro-4-oxochroman-3-yl)-2-oxoacetate | 503301-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: ethyl 2-(6-fluoro-4-oxochroman-3-yl)-2-oxoacetate
• 英文别名: ethyl 2-(6-fluoro-4-oxo-2,3-dihydrochromen-3-yl)-2-oxoacetate
• CAS: 503301-16-4
• 化学式: C₁₃H₁₁FO₅
• 分子量: 266.226
• InChiKey: YFDBSACMHIFDGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-(6-fluoro-4-oxochroman-3-yl)-2-oxoacetate 在 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成
  参考文献：
  名称：

  Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis

  摘要：

  Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, and fibrosis. While there are currently no approved therapies for NASH, the bile acid-derived FXR agonist obeticholic acid (OCA; 6-ethyl chenodeoxycholic acid) has shown promise in clinical studies. Previously, we described the discovery of tropifexor (LJN452), the most potent non-bile acid FXR agonist currently in clinical investigation. Here, we report the discovery of a novel chemical series of non-bile acid FXR agonists based on a tricyclic dihydrochromenopyrazole core from which emerged nidufexor (LMB763), a compound with partial FXR agonistic activity in vitro and FXR-dependent gene modulation in vivo. Nidufexor has advanced to Phase 2 human clinical trials in patients with NASH and diabetic nephropathy.

  DOI：

  10.1021/acs.jmedchem.9b01621
• 作为产物：
  描述：

  6-氟-4-二氢色原酮 、 草酸二乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 0.17h， 以66.2%的产率得到ethyl 2-(6-fluoro-4-oxochroman-3-yl)-2-oxoacetate
  参考文献：
  名称：

  [EN] TRICYCLIC COMPOUNDS AS GLUTAMATE RECEPTOR MODULATORS
  [FR] COMPOSÉS TRICYCLIQUES COMME MODULATEURS DES RÉCEPTEURS DE GLUTAMATES

  摘要：

  本文披露的是可能是代谢型受体亚型5的负性别构调节剂的化合物，以及制备和使用这些化合物的方法。

  公开号：

  WO2010049366A1

文献信息

• TRICYCLIC COMPOUNDS AS GLUTAMATE RECEPTOR MODULATORS
  申请人：Bertinato Peter

  公开号：US20110263588A1

  公开（公告）日：2011-10-27

  The present invention relates to compounds that may be negative allosteric modulators of metabotropic receptors-subtype 5, and methods of making and using same.

  本发明涉及可能是代谢型受体亚型5的负向变构调节剂的化合物，以及制备和使用它们的方法。
• SUBSTITUTED PYRAZOLO COMPOUNDS FOR THE TREATMENT OF INFLAMMATION
  申请人：Pharmacia Corporation

  公开号：EP1427706B1

  公开（公告）日：2007-05-30
• US7211597B2
  申请人：——

  公开号：US7211597B2

  公开（公告）日：2007-05-01
• [EN] TRICYCLIC COMPOUNDS AS GLUTAMATE RECEPTOR MODULATORS<br/>[FR] COMPOSÉS TRICYCLIQUES COMME MODULATEURS DES RÉCEPTEURS DE GLUTAMATES
  申请人：GLAXO GROUP LTD

  公开号：WO2010049366A1

  公开（公告）日：2010-05-06

  Disclosed herein are compounds that may be negative allosteric modulators of metabotropic receptors-subtype 5, and methods of making and using same.

  本文披露的是可能是代谢型受体亚型5的负性别构调节剂的化合物，以及制备和使用这些化合物的方法。
• Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis
  作者：Donatella Chianelli、Paul V. Rucker、Jason Roland、David C. Tully、John Nelson、Xiaodong Liu、Badry Bursulaya、Eloy D. Hernandez、Jane Wu、Mahavir Prashad、Thierry Schlama、Yugang Liu、Alan Chu、James Schmeits、David J. Huang、Robert Hill、Dingjiu Bao、Jocelyn Zoll、Young Kim、Todd Groessl、Peter McNamara、Bo Liu、Wendy Richmond、Ignacio Sancho-Martinez、Andrew Phimister、H. Martin Seidel、Michael K. Badman、Sean B. Joseph、Bryan Laffitte、Valentina Molteni

  DOI：10.1021/acs.jmedchem.9b01621

  日期：2020.4.23

  Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, and fibrosis. While there are currently no approved therapies for NASH, the bile acid-derived FXR agonist obeticholic acid (OCA; 6-ethyl chenodeoxycholic acid) has shown promise in clinical studies. Previously, we described the discovery of tropifexor (LJN452), the most potent non-bile acid FXR agonist currently in clinical investigation. Here, we report the discovery of a novel chemical series of non-bile acid FXR agonists based on a tricyclic dihydrochromenopyrazole core from which emerged nidufexor (LMB763), a compound with partial FXR agonistic activity in vitro and FXR-dependent gene modulation in vivo. Nidufexor has advanced to Phase 2 human clinical trials in patients with NASH and diabetic nephropathy.