4-(2-氟苯基)-3-氧代丁酸乙酯 | 221121-35-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(2-氟苯基)-3-氧代丁酸乙酯
• 英文名称: ethyl 4-(2-fluorophenyl)-3-oxobutanoate
• CAS: 221121-35-3
• 化学式: C₁₂H₁₃FO₃
• 分子量: 224.232
• InChiKey: ULGNQPPGNKYLFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-氟苯基)-3-氧代丁酸乙酯 在 sodium ethanolate 、 caesium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 ethyl 5-(2-fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxylate
  参考文献：
  名称：

  Pyridone Derivatives

  摘要：

  提供了抑制Axl并用于治疗由Axl高功能引起的疾病、与Axl高功能相关的疾病和/或伴随Axl高功能的疾病的新型化合物或其盐，或其晶体。提供了由式（1）所代表的吡啶酮衍生物，具有各种取代基或其盐，或其晶体（其中式（1）中的R1、R2、R3、R5、R6、A、W、X和n分别如规范中定义）。

  公开号：

  US20130281428A1
• 作为产物：
  描述：

  邻氟苯乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 4-(2-氟苯基)-3-氧代丁酸乙酯
  参考文献：
  名称：

  Bioisosteric replacement of an acylureido moiety attached to an indolin-2-one scaffold with a malonamido or a 2/4-pyridinoylamido moiety produces a selectively potent Aurora-B inhibitor

  摘要：

  Bioisosteric replacement of acylureido moiety in 6-acylureido-3-pyrrolylmethylidene-2-oxoindoline derivatives resulted in a series of malonamido derivatives with indolin-2-one scaffold (11-14). Further conformational restrictions of the malonamido moiety led to 2-oxo-1,2-dihydropyridine (21-25) or a 4-oxo-1,4-dihydropyridine derivatives (31-36). 4-Oxo-1,4-dihydropyridine derivatives were more potent Aurora B inhibitors than their 2-oxo-1,2-dihydropyridine counterparts and demonstrated cytotoxicities against A549 and HepG2 cells in the submicromolar range. In A549 cells, 31h decreased phosphorylation of histone H3, triggered polyploidy, induced expression of pro-apoptotic Fas and FasL with subsequent activation of caspase 8, resulting into apoptosis. In a Huh7-xenograft mouse model, 31h demonstrated potent in vivo efficacy with a daily dose of 5 mg/kg.

  DOI：

  10.1016/j.ejmech.2014.07.033

文献信息

• Pyridone derivatives
  申请人：Daiichi Sankyo Company, Limited

  公开号：US08933103B2

  公开（公告）日：2015-01-13

  Novel compounds or salts thereof, or crystals thereof, which inhibit Axl and are useful for treating diseases caused by Axl hyperfunction, diseases associated with Axl hyperfunction and/or diseases accompanied by Axl hyperfunction are provided. Pyridone derivatives represented by the formula (1) having various substituents or salts thereof, or crystals thereof (where R1, R2, R3, R5, R6, A, W, X and n in the formula (1) are as defined in the specification, respectively) are provided.

  提供了抑制Axl并用于治疗由Axl高功能引起的疾病，与Axl高功能相关的疾病和/或伴随Axl高功能的疾病的新型化合物或其盐或晶体。提供了具有各种取代基的式（1）所代表的吡啶酮衍生物或其盐或晶体（其中式（1）中的R1、R2、R3、R5、R6、A、W、X和n在规范中分别定义）。
• SGC STIMULATORS
  申请人：NAKAI Taakshi

  公开号：US20150232461A1

  公开（公告）日：2015-08-20

  The present patent application discloses at least the compounds according to Formula I or Formula Ib shown below, or pharmaceutically acceptable salts thereof, wherein ring B, J B , n, J D , J, o, X, R C and R A are as described herein.

  本专利申请披露了至少按照下面的公式I或公式Ib所示的化合物，或其药学上可接受的盐，其中，环B、JB、n、JD、J、o、X、RC和RA的描述如下。
• Discovery and Optimization of Triazolopyrimidinone Derivatives as Selective NLRP3 Inflammasome Inhibitors
  作者：David Harrison、Mark G. Bock、John R. Doedens、Christopher A. Gabel、M. Katharine Holloway、Arwel Lewis、Jane Scanlon、Andrew Sharpe、Iain D. Simpson、Pamela Smolak、Grant Wishart、Alan P. Watt

  DOI：10.1021/acsmedchemlett.2c00242

  日期：2022.8.11

  osteoarthritis, and gout. The discovery of potent and specific NLRP3 inhibitors could reduce the burden of several common morbidities. In this study, we identified a weakly potent triazolopyrimidone hit (1) following an in silico modeling exercise. This was optimized to furnish potent and selective small molecule NLRP3 inflammasome inhibitors. Compounds such as NDT-30805 could be useful tool molecules

  NLRP3 炎症小体是一种多蛋白复合物，可促进促炎细胞因子白介素-1β (IL-1β) 和 IL-18 响应感染或内源性刺激而激活和释放。它可能被一系列危险信号不当激活，导致多种疾病的慢性、低度炎症，如阿尔茨海默病、帕金森病、骨关节炎和痛风。有效且特异性的 NLRP3 抑制剂的发现可以减轻几种常见疾病的负担。在这项研究中，我们在计算机建模练习后发现了一种弱效的三唑并嘧啶酮 ( 1 ) 。经过优化，可提供有效且选择性的小分子 NLRP3 炎性体抑制剂。NDT-30805等化合物可能是支架跳跃或药效团生成项目的有用工具分子，或用作临床候选药物开发的先导。
• 5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3<i>H</i>)-ones:  Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives
  作者：Antonello Mai、Marino Artico、Gianluca Sbardella、Silvio Massa、Ettore Novellino、Giovanni Greco、Anna Giulia Loi、Enzo Tramontano、Maria Elena Marongiu、Paolo La Colla

  DOI：10.1021/jm980260f

  日期：1999.2.1

  Molecular modeling analysis of compounds belonging to the recently published series of dihydroalkoxy-benzyl-oxopyrimidines (DABOs), such as S-DABOs and DATNOs, gave support to the design of new 2,6-disubstituted benzyl-DABO derivatives as highly potent and specific inhibitors of the HIV-1 reverse transcriptase (RT). To follow up on the novel DABO derivatives, we decided to investigate the effect of electron-withdrawing substituents in the benzyl unit of the S-DABO skeleton versus their anti-HIV-1 activity. Such chemical modifications impacted the inhibitory activity, especially when two halogen units were introduced at positions 2 and 6 in the phenyl portion of the benzyl group bound to C-6 of the pyrimidine ring. Various 5-alkyl-2-(alkyl(or cycloalkyl)thio)-6-(2,B-dichloro(or 2, 6-difluoro)phenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones were then synthesized and tested as anti-HIV-1 agents in both cell-based and enzyme (recombinant reverse transcriptase, rRT) assays. Among the various mono- and disubstituted phenyl derivatives, the most potent were those containing a 6-(2,6-difluorophenylmethyl) substituent (F-DABOs), which showed EC50's ranging between 40 and 90 nM and selectivity indexes up to greater than or equal to 5000. An excellent correlation was found between EC50 and IC50 values which confirmed that these compounds act as inhibitors of the HIV-1 RT. The structure-activity relationships of the newly synthesized pyrimidinones are presented herein.
• PYRIDONE DERIVATIVE
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2810937B1

  公开（公告）日：2016-11-30