3-氧代-2-(4-(三氟甲基)苯基)丁酸乙酯 | 1068516-41-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 3-氧代-2-(4-(三氟甲基)苯基)丁酸乙酯
• 英文名称: ethyl 3-oxo-2-(4-(trifluoromethyl)phenyl)butanoate
• 英文别名: ethyl 3-oxo-2-[4-(trifluoromethyl)phenyl]butanoate
• CAS: 1068516-41-5
• 化学式: C₁₃H₁₃F₃O₃
• 分子量: 274.24
• InChiKey: IMBONOQGDCJTGP-UHFFFAOYSA-N

物化性质

• 沸点：
  298.4±35.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-氧代-2-(4-(三氟甲基)苯基)丁酸乙酯 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 6-chloro-7-methoxy-2-methyl-3-(4-(trifluoromethyl)phenyl)-quinolin-4(1H)-one
  参考文献：
  名称：

  具有 pH 触发释放机制的氨基烷氧基羰基氧基甲基醚前药：通过单剂量治疗提高抗疟药 4(1H)-喹诺酮类药物的溶解度、生物利用度和功效的案例研究

  摘要：

  许多小分子的临床前和临床开发因其水溶性差、吸收有限和口服生物利用度而受到阻碍。在此，我们公开了一种通用的前药方法，该方法将有前景的先导化合物转化为氨基烷氧基羰基氧基甲基（氨基 AOCOM）醚取代的类似物，显示出显着改善的水溶性和增强的口服生物利用度，恢复了候选药物的典型关键要求。前药完全独立于生物转化和动物独立，因为它通过 pH 触发的分子内环化 - 消除反应成为活性化合物。作为概念验证，这种新型氨基 AOCOM 醚前药方法的效用在代表多种抗疟药 4(1H )-喹诺酮类药物，在过去十年中进入临床前开发并失败。使用氨基 AOCOM 醚前药部分，3-aryl-4(1 H )-喹诺酮类临床前候选药物显示在啮齿动物疟疾模型中以 3 mg/kg 的口服剂量提供单剂量治疗，而无需使用先进的配方技术。

  DOI：

  10.1021/acs.jmedchem.0c01104
• 作为产物：
  描述：

  (4-trifluoromethylphenyl)(phenyl)iodonium triflate 、 乙酰乙酸乙酯 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以89%的产率得到3-氧代-2-(4-(三氟甲基)苯基)丁酸乙酯
  参考文献：
  名称：

  Metal-Free Arylation of Ethyl Acetoacetate with Hypervalent Diaryliodonium Salts: An Immediate Access to Diverse 3-Aryl-4(1H)-Quinolones

  摘要：

  A clean arylation protocol of ethyl acetoacetate was developed using hypervalent diaryliodonium salts under mild and metal-free conditions. The scope of the reaction, using symmetric and unsymmetric iodonium salts with varying sterics and electronics, was examined. Further, this method has been applied for the synthesis of antimalarial compound ELQ-300, which is currently in preclinical development.

  DOI：

  10.1021/jo5023958

文献信息

• Discovery and structure–activity relationship of coumarin derivatives as TNF-α inhibitors
  作者：Jie-Fei Cheng、Mi Chen、David Wallace、Sovouthy Tith、Thomas Arrhenius、Hirotaka Kashiwagi、Yoshiyuki Ono、Akira Ishikawa、Haruhiko Sato、Toshiro Kozono、Hediki Sato、Alex M. Nadzan

  DOI：10.1016/j.bmcl.2004.03.022

  日期：2004.5

  The discovery and structure-activity relationship of a novel series of coumarin-based TNF-alpha inhibitors is described. Starting from the initial lead la, various derivatives were prepared surrounding the coumarin core structure to optimize the in vitro inhibitory activity of TNF-alpha production by human peripheral blood mononuclear cells (hPBMC), stimulated by bacterial lipopolysaccharide (LPS). Selected compounds also demonstrated in vivo inhibition of TNF-alpha production in rats. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of substituted pyrazoles as blockers of divalent metal transporter 1 (DMT1)
  作者：Jay A. Cadieux、Zaihui Zhang、Maryanne Mattice、Alison Brownlie-Cutts、Jianmin Fu、Laszlo G. Ratkay、Rainbow Kwan、Jay Thompson、Joseph Sanghara、Jing Zhong、Y. Paul Goldberg

  DOI：10.1016/j.bmcl.2011.11.069

  日期：2012.1

  Three distinct series of substituted pyrazole blockers of divalent metal transporter 1 (DMT1) were elaborated from the high-throughput screening pyrazolone hit 1. Preliminary hit-to-lead efforts revealed a preference for electron-withdrawing substituents in the 4-amido-5-hydroxypyrazole series 6a-l. In turn, this preference was more pronounced in a series of 4-aryl-5-hydroxypyrazoles 8a-j. The representative analogs 6f and 12f were found to be efficacious in a rodent model of acute iron hyperabsorption. These three series represent promising starting points for lead optimization efforts aimed at the discovery of DMT1 blockers as iron overload therapeutics. (C) 2011 Elsevier Ltd. All rights reserved.
• WO2008/121861
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] PYRAZOLE AND PYRROLE COMPOUNDS USEFUL IN TREATING IRON DISORDERS<br/>[FR] COMPOSÉS À BASE DE PYRAZOLE ET DE PYRROLE UTILES DANS LE TRAITEMENT DE TROUBLES DU MÉTABOLISME DU FER
  申请人：XENON PHARMACEUTICALS INC

  公开号：WO2008121861A2

  公开（公告）日：2008-10-09

  [EN] This invention is directed to pyrazole and pyrrole compounds, for example, compounds of formula (I): wherein R¹, R², R³ and R⁴ are as defined herein, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of iron disorders. This invention is also directed to pharmaceutical compositions comprising the compounds and methods of using the compounds to treat iron disorders.
  [FR] L'invention concerne des composés à base de pyrazole et de pyrrole, par exemples des composés de formule (I) où R¹, R², R³ et R⁴ sont tels que définis dans la description, tels que leurs stéréoisomères, énantiomères, tautomères ou leurs mélanges, ou sels pharmaceutiquement acceptables, leurs solvates ou promédicaments, destinés au traitement de troubles du métabolisme du fer. L'invention concerne également des compositions pharmaceutiques renfermant ces composés et des procédés d'utilisation de ces composés pour traiter les troubles du métabolisme du fer.