4,4-二氟-1-(4-甲基苯基)丁烷-1,3-二酮 | 165328-11-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4,4-二氟-1-(4-甲基苯基)丁烷-1,3-二酮
• 英文名称: 4,4-Difluoro-1-(4-methylphenyl)butane-1,3-dione
• CAS: 165328-11-0
• 化学式: C₁₁H₁₀F₂O₂
• mdl: MFCD03419779
• 分子量: 212.196
• InChiKey: JPMQITHKRYMPHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,4-二氟-1-(4-甲基苯基)丁烷-1,3-二酮 在 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 ethyl (5R,7S)-7-(difluoromethyl)-5-(4-methylphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylate
  参考文献：
  名称：

  发现四氢吡唑并嘧啶羧酰胺衍生物作为有效的和口服活性的抗结核药。

  摘要：

  从结核分枝杆菌（Mtb）全细胞高通量筛选（HTS）活动中鉴定了四氢吡唑并[1,5-a]嘧啶支架是一个热门系列。合成了这类的一系列衍生物，以评估它们的结构-活性关系（SAR）和结构-性质关系（SPR）。化合物9在小鼠中具有有希望的体内DMPK谱，并且在小鼠功效模型中表现出有效的体内活性，在以100 mg / kg的剂量每天口服一次给予感染小鼠28天后，实现了Mtb的3.5 log CFU降低。因此，化合物9是药物敏感性和耐药性TB的联合疗法中潜在的候选药物。

  DOI：

  10.1021/ml400071a
• 作为产物：
  描述：

  二氟乙酸乙酯 、 对甲基苯乙酮 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 4,4-二氟-1-(4-甲基苯基)丁烷-1,3-二酮
  参考文献：
  名称：

  发现四氢吡唑并嘧啶羧酰胺衍生物作为有效的和口服活性的抗结核药。

  摘要：

  从结核分枝杆菌（Mtb）全细胞高通量筛选（HTS）活动中鉴定了四氢吡唑并[1,5-a]嘧啶支架是一个热门系列。合成了这类的一系列衍生物，以评估它们的结构-活性关系（SAR）和结构-性质关系（SPR）。化合物9在小鼠中具有有希望的体内DMPK谱，并且在小鼠功效模型中表现出有效的体内活性，在以100 mg / kg的剂量每天口服一次给予感染小鼠28天后，实现了Mtb的3.5 log CFU降低。因此，化合物9是药物敏感性和耐药性TB的联合疗法中潜在的候选药物。

  DOI：

  10.1021/ml400071a

文献信息

• Design, Synthesis, Herbicidal Activity, and Structure–Activity Relationship Study of Novel 6-(5-Aryl-Substituted-1-Pyrazolyl)-2-Picolinic Acid as Potential Herbicides
  作者：Tong Feng、Qing Liu、Zhi-Yuan Xu、Hui-Ting Li、Wei Wei、Rong-Chuan Shi、Li Zhang、Yi-Ming Cao、Shang-Zhong Liu

  DOI：10.3390/molecules28031431

  日期：——

  were designed and synthesized for the discovery of compounds with potent herbicidal activity. The compounds were tested for inhibitory activity against the growth of Arabidopsis thaliana roots, and the results demonstrated that the IC50 value of compound V-7 was 45 times lower than that of the halauxifen-methyl commercial herbicide. Molecular docking analyses revealed that compound V-7 docked with the

  吡啶甲酸和吡啶甲酸盐化合物是一类卓越的合成植物生长素除草剂。近年来，两种新的吡啶甲酸酯类化合物甲基卤昔芬（ArylexTM 活性）和氟吡唑醚苄基（RinskorTM 活性）已作为新型除草剂上市。以其结构骨架为模板，设计合成了33个4-amino-3,5-dicholor-6-(5-aryl-substituted-1-pytazolyl)-2-picolinic acid化合物，用于发现具有强效除草作用的化合物活动。测试化合物对拟南芥根部生长的抑制活性，结果表明化合物V-7的IC50值比商业除草剂halauxifen-methyl低45倍。分子对接分析表明，化合物 V-7 与受体生长素信号转导 F-box 蛋白 5 (AFB5) 的对接比毒草胺更密集。根据这些 IC50 值构建自适应三维定量构效关系模型，以指导下一步的合成策略。新化合物的除草试验表明，化合物V-8在300 gha-1剂量下
• ——
  作者：K. I. Pashkevich、D. V. Sevenard、O. G. Khomutov、I. I. Vorontsov

  DOI：10.1023/a:1011317013265

  日期：——

  An efficient procedure for the synthesis of 3-cyano-4-difluoromethyl- and 3-cyano-4-trifluoromethyl-2(1H)-pyridones was developed. The structure of one of the resulting compounds was established by X-ray diffraction analysis.
• Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine
  作者：Jin Li、Kristin M.Lundy DeMello、Henry Cheng、Subas M. Sakya、Brian S. Bronk、Robert J. Rafka、Burton H. Jaynes、Carl B. Ziegler、Carolyn Kilroy、Donald W. Mann、Eric L. Nimz、Michael P. Lynch、Michelle L. Haven、Nicole L. Kolosko、Martha L. Minich、Chao Li、Jason K. Dutra、Bryson Rast、Rhonda M. Crosson、Barry J. Morton、Glen W. Kirk、Kathleen M. Callaghan、David A. Koss、Andrei Shavnya、Lisa A. Lund、Scott B. Seibel、Carol F. Petras、Annette Silvia

  DOI：10.1016/j.bmcl.2003.10.004

  日期：2004.1

  Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted. (C) 2003 Elsevier Ltd. All rights reserved.
• 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.
• Synthesis and SAR/3D-QSAR studies on the COX-2 inhibitory activity of 1,5-diarylpyrazoles to validate the modified pharmacophore
  作者：Sunil K. Singh、V. Saibaba、K. Srinivasa Rao、P. Ganapati Reddy、Pankaj R. Daga、S. Abdul Rajjak、Parimal Misra、Y. Koteswar Rao

  DOI：10.1016/j.ejmech.2005.03.016

  日期：2005.10

  Diverse analogs of 1,5-diarylpyrazoles having 3-hydroxymethyl-4-sulfamoyl (SO2NH2)/methyl sulfonyl (SO2Me)-pheny group at N-1 were synthesized and evaluated for their in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The SAR study mainly involved the variations at positions C-3, C-5 and N-1 of the pyrazole ring. Several small hydrophobic groups at/around position-4 of C-5 phenyl, viz. 3,4-dimethylphenyl analog 9, 3-methyl-4-methylsulfanylphenyl analog 14 and 2,3-dihydrobenzo[b]thiophenyl analog 17, exhibited impressive COX-2 inhibitory potency. In general, the sulfonamide analogues with a CHF2 at C-3 were found to be more potent than those having a CF3 group. The three dimensional quantitative structure activity relationship comprising comparative molecular field analysis (3D-QSAR-CoMFA) afforded the models with high predictivity which further validated the acceptance of hydroxymethyl (CH2OH) group in the hydrophilic pocket of the COX-2 enzyme. (c) 2005 Elsevier SAS. All rights reserved.