4,4,4-trifluoro-1-(2-nitrophenyl)butane-1,3-dione | 35999-52-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4,4,4-trifluoro-1-(2-nitrophenyl)butane-1,3-dione
• CAS: 35999-52-1
• 化学式: C₁₀H₆F₃NO₄
• mdl: MFCD11542787
• 分子量: 261.157
• InChiKey: ONQLWSTWOUGITA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  80
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4,4,4-trifluoro-1-(2-nitrophenyl)butane-1,3-dione 在 palladium on activated charcoal 一水合肼 作用下， 以 乙醇 为溶剂， 反应 34.5h， 生成 4-[5-(2-Aminophenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors:  Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib)

  摘要：

  A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of ii (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

  DOI：

  10.1021/jm960803q
• 作为产物：
  描述：

  邻硝基苯乙酮 、 三氟乙酸乙酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 4,4,4-trifluoro-1-(2-nitrophenyl)butane-1,3-dione
  参考文献：
  名称：

  使用便利的荧光成像酶标仪分析法对羟基三氟甲基吡唑啉作为Orai1介导的Ca 2+进入MDA-MB-231乳腺癌细胞的抑制剂的SAR研究

  摘要：

  蛋白质Orai1和STIM1控制存储操作的Ca 2+进入（SOCE）进入细胞。SOCE对于MDA-MB-231人三阴性乳腺癌（TNBC）细胞的迁移，侵袭和转移很重要，并且已被提议作为癌症药物发现的靶标。通过荧光成像板读数器（FLIPR）Ca 2+测量，中等通量筛选中的两种命中化合物显示出令人鼓舞的MDA-MB-231细胞中SOCE抑制作用分析。在对这些命中进行NMR光谱分析并将其结构重新分配为5-羟基-5-三氟甲基吡唑啉之后，通过取代的酰基hydr与三氟甲基1,3-二羰基芳烃之间的热缩合反应，制备了一系列类似物。结构-活性关系（SAR）研究表明，RHS的2和3位以及LHS末端苯环的2、3和4位上的小亲脂性取代基提高了活性，从而产生了一类新的强效和选择性的SOCE抑制剂。

  DOI：

  10.1016/j.bmc.2018.05.012

文献信息

• A solvent-free, base-catalyzed domino reaction towards trifluoromethylated benzenes from bio-based methyl coumalate
  作者：Liang Chang、Nadja Klipfel、Luc Dechoux、Serge Thorimbert

  DOI：10.1039/c7gc03721j

  日期：——

  CO2 and water are the only byproducts of this process, and the reaction conditions can scale up to gram quantities. The transformation involves an unprecedented tBuOK-catalyzed domino process, and features Michael addition/6π-electrocyclic ring opening/[1,5]-H shift/carba-6π-electrocyclic ring closure/decarboxylative aromatization reactions.

  报道了一种用于CF 3取代的苯生产的新颖，有效且与环境相容的方法。它以生物基原料为原料，使用t BuOK作为催化剂，并且不含溶剂。这种区域选择性的方法可以很好地提供各种三氟甲基苯，而无需任何额外的氧化剂或特别的照顾。CO 2和水是该过程的唯一副产物，反应条件可以扩展到克量。该转化涉及前所未有的t BuOK催化的多米诺骨牌过程，并具有迈克尔加成/6π-电环开环/ [1,5] -H移位/carba-6π-电环闭环/脱羧芳构化反应。
• Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors:  Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1<i>H</i>-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib)
  作者：Thomas D. Penning、John J. Talley、Stephen R. Bertenshaw、Jeffery S. Carter、Paul W. Collins、Stephen Docter、Matthew J. Graneto、Len F. Lee、James W. Malecha、Julie M. Miyashiro、Roland S. Rogers、D. J. Rogier、Stella S. Yu、Gary D. Anderson、Earl G. Burton、J. Nita Cogburn、Susan A. Gregory、Carol M. Koboldt、William E. Perkins、Karen Seibert、Amy W. Veenhuizen、Yan Y. Zhang、Peter C. Isakson

  DOI：10.1021/jm960803q

  日期：1997.4.1

  A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of ii (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.
• An SAR study of hydroxy-trifluoromethylpyrazolines as inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader assay
  作者：Ralph J. Stevenson、Iman Azimi、Jack U. Flanagan、Marco Inserra、Irina Vetter、Gregory R. Monteith、William A. Denny

  DOI：10.1016/j.bmc.2018.05.012

  日期：2018.7

  structures as 5-hydroxy-5-trifluoromethylpyrazolines, a series of analogues was prepared via thermal condensation reactions between substituted acylhydrazones and trifluoromethyl 1,3-dicarbonyl arenes. Structure-activity relationship (SAR) studies showed that small lipophilic substituents at the 2- and 3-positions of the RHS and 2-, 3- and 4-postions of the LHS terminal benzene rings improved activity

  蛋白质Orai1和STIM1控制存储操作的Ca 2+进入（SOCE）进入细胞。SOCE对于MDA-MB-231人三阴性乳腺癌（TNBC）细胞的迁移，侵袭和转移很重要，并且已被提议作为癌症药物发现的靶标。通过荧光成像板读数器（FLIPR）Ca 2+测量，中等通量筛选中的两种命中化合物显示出令人鼓舞的MDA-MB-231细胞中SOCE抑制作用分析。在对这些命中进行NMR光谱分析并将其结构重新分配为5-羟基-5-三氟甲基吡唑啉之后，通过取代的酰基hydr与三氟甲基1,3-二羰基芳烃之间的热缩合反应，制备了一系列类似物。结构-活性关系（SAR）研究表明，RHS的2和3位以及LHS末端苯环的2、3和4位上的小亲脂性取代基提高了活性，从而产生了一类新的强效和选择性的SOCE抑制剂。