4-fluoro-4'-(methylsulfonyl)benzil | 157671-97-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 4-fluoro-4'-(methylsulfonyl)benzil
• 英文别名: 4-fluoro-4'-methanesulfonylbenzil；1-(4-Methylsulfonylphenyl)-2-(4-fluorophenyl)-ethane-1,2-dione；1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethane-1,2-dione
• CAS: 157671-97-1
• 化学式: C₁₅H₁₁FO₄S
• 分子量: 306.314
• InChiKey: UKEKDJVEOZLJCQ-UHFFFAOYSA-N

物化性质

• 沸点：
  517.4±50.0 °C(predicted)
• 密度：
  1.353±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-fluoro-4'-(methylsulfonyl)benzil 在 palladium on activated charcoal 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 2-(4-Fluoro-phenyl)-3-(4-methanesulfonyl-phenyl)-pyrazine
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,3-diarylpyrazines and quinoxalines as selective COX-2 inhibitors

  摘要：

  Several 2,3-diaryl pyrazines and quinoxalines with 4-sulfamoyl (SO2NH2)/methylsulfonyl (SO2Me)-phenyl pharmaco-phores have been synthesized and evaluated for the cyclooxygenase (COX-1/COX-2) inhibitory activity. Smaller groups such as methoxy, methyl and fluoro when substituted at/around position-4 of the adjacent phenyl ring, have great impact on the selective COX-2 inhibitory activity of the series. Many potential compounds were obtained from a brief structure-activity relationship (SAR) study. Two of these, compounds 11 and 25 exhibited excellent in vivo activity in the established animal model of inflammation. Since compound 25 possessed an amenable sulfonamide group, two of its prodrugs 48 and 49 were also synthesized. Both of them have excellent in vivo potential, and represent a new class of COX-2 inhibitor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.01.033
• 作为产物：
  描述：

  对氟苯乙酰氯 在 三氯化铝 、 selenium(IV) oxide 、 双氧水 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 4-fluoro-4'-(methylsulfonyl)benzil
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,3-diarylpyrazines and quinoxalines as selective COX-2 inhibitors

  摘要：

  Several 2,3-diaryl pyrazines and quinoxalines with 4-sulfamoyl (SO2NH2)/methylsulfonyl (SO2Me)-phenyl pharmaco-phores have been synthesized and evaluated for the cyclooxygenase (COX-1/COX-2) inhibitory activity. Smaller groups such as methoxy, methyl and fluoro when substituted at/around position-4 of the adjacent phenyl ring, have great impact on the selective COX-2 inhibitory activity of the series. Many potential compounds were obtained from a brief structure-activity relationship (SAR) study. Two of these, compounds 11 and 25 exhibited excellent in vivo activity in the established animal model of inflammation. Since compound 25 possessed an amenable sulfonamide group, two of its prodrugs 48 and 49 were also synthesized. Both of them have excellent in vivo potential, and represent a new class of COX-2 inhibitor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.01.033

文献信息

• Novel Terphenyls as Selective Cyclooxygenase-2 Inhibitors and Orally Active Anti-inflammatory Agents
  作者：James J. Li、Monica B. Norton、Emily J. Reinhard、Gary D. Anderson、Susan A. Gregory、Peter C. Isakson、Carol M. Koboldt、Jaime L. Masferrer、William E. Perkins、Karen Seibert、Yan Zhang、Ben S. Zweifel、David B. Reitz

  DOI：10.1021/jm950878e

  日期：1996.1.1

  The sulfonamide analogs 17 and 21 were found to be much more potent COX-2 inhibitors and orally active anti-inflammatory agents than the corresponding methyl sulfone analogs 16 and 20, respectively, albeit with some decrease in COX-2 selectivity. Structure-activity relationship studies have determined that incorporation of two fluorine atoms in the central phenyl group, as in 20 and 21, is extremely

  一系列新的三联苯甲基砜和磺酰胺已被证明是高效的选择性环氧合酶2（COX-2）抑制剂。发现磺酰胺类似物17和21分别比相应的甲基砜类似物16和20更有效的COX-2抑制剂和口服活性抗炎药，尽管COX-2选择性有所降低。结构-活性关系研究已经确定，在中央苯基中引入两个氟原子（如20和21）对于体外COX-2的效力和选择性以及体内活性都极为有利。1,2-二芳基-4,5-二氟苯磺酰胺系列中几个值得注意的例子是21a-c，k，l，n（COX-2，IC50 = 0.002-0.004 microM），其中所有都具有体外COX-1 / COX-2选择性>1000。此外，在炎症的气袋模型中，磺酰胺21a，b，d，g，j，m，n，q显示出大大增强的口服活性，并抑制了90％以上的前列腺素E2产生。此外，在大鼠佐剂诱导的关节炎模型（ED50 = 0.05 mg / kg）和角叉菜胶诱导的痛觉过敏试验（ED50 =
• Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors
  作者：Thomas E. Barta、Michael A. Stealey、Paul W. Collins、Richard M. Weier

  DOI：10.1016/s0960-894x(98)00627-1

  日期：1998.12

  The synthesis and activity of a series of 4,5-diarylimidazole analogs are described. One analog had an IC50 of 80 nM, was 6750-selective against COX-1, and demonstrated in vivo potency in the mouse air pouch model.

  描述了一系列4,5-二芳基咪唑类似物的合成和活性。一种类似物的IC50为80 nM，对COX-1具有6750选择性，并在小鼠气袋模型中显示出体内效力。
• Method of treating skin related conditions
  申请人：G. D. Searle & Co.

  公开号：US06274590B1

  公开（公告）日：2001-08-14

  A class of 3,4-diaryl substituted thiophene, derivatives and analogs thereof, pharmaceutical compositions containing them and methods of using them to treat inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I: wherein Y is S; wherein X is one or two substituents selected from hydrido, halo, lower alkoxycarbonyl and carboxyl; wherein R2 and R3 are independently aryl or heteroaryl; and wherein R2 and R3 are optionally substituted with one or more radicals selected from sulfamyl, alkylsulfonyl, halo, lower alkoxy and lower alkyl; or a pharmaceutically-acceptable salt thereof.

  一种3,4-二芳基取代噻吩类，其衍生物和类似物，包含它们的制药组合物以及使用它们治疗炎症和炎症相关疾病的方法。特别感兴趣的化合物由式I定义：其中Y为S；其中X为从氢基，卤素，低烷氧基羰基和羧基中选择的一个或两个取代基；其中R2和R3分别为芳基或杂环芳基；其中R2和R3可以选择地用来自磺酰胺基，烷基磺酰基，卤素，低烷氧基和低烷基的一个或多个基团取代；或其药学上可接受的盐。
• [EN] 4,5-SUBSTITUTED IMIDAZOLYL COMPOUNDS FOR THE TREATMENT OF INFLAMMATION<br/>[FR] COMPOSES D'IMIDAZOLYLE SUBSTITUES EN POSITIONS 4 ET 5, CONVENANT AU TRAITEMENT DE L'INFLAMMATION
  申请人：G.D. SEARLE & CO.

  公开号：WO1996003387A1

  公开（公告）日：1996-02-08

  (EN) A class of compounds is described for treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (I), wherein R1 is selected from lower alkyl, lower haloalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower alkenyloxyalkyl, mercapto, lower alkylcarbonyl, lower haloalkylcarbonyl, phenylcarbonyl, lower aralkylcarbonyl, lower aralkenyl, lower aryloxyalkyl, lower aralkyloxyalkyl, lower arylsulfonyl, lower aralkylsulfonyl, lower arylthioalkyl, lower heteroarylalkylthioalkyl, and heteroaryl selected from 2-thienyl, 2-furyl, 3-furyl, 2-pyridyl, 4-pyridyl and 2-benzofuryl; wherein R2 and R3 are independently selected from heteroaryl, cycloalkyl and aryl, wherein the heteroaryl, cycloalkyl and aryl radicals are substituted at a substitutable position with one or more radicals selected from hydrido, halo, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, aminosulfonyl, lower alkyl, cyano, carboxyl, lower alkoxycarbonyl, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, lower haloalkoxy, amino, lower alkylamino, phenylamino and nitro; and wherein R4 is selected from hydrido, lower alkyl and acyl; or a pharmaceutically acceptable salt thereof.(FR) La présente invention concerne une classe de composés convenant au traitement de l'inflammation et des troubles liés à l'inflammation. Les composés concernés en l'occurrence sont décrits par la formule générale (I). Dans cette formule générale (I), 'R1' est choisi parmi alkyle inférieur, haloalkyle inférieur, hydroxyalkyle inférieur, alcoxyalkyle inférieur, alcényloxyalkyle inférieur, mercapto, alkylcarbonyle inférieur, haloalkylcarbonyle inférieur, phénylcarbonyle, aralkylcarbonyle inférieur, aralcényle inférieur, aryloxyalkyle inférieur, aralkyloxyalkyle inférieur, arylsulfonyle inférieur, aralkylsulfonyle inférieur, arylthioalkyle inférieur, hétéroarylalkylthioalkyle inférieur, et hétéroaryle choisi parmi 2-thiényle, 2-furyle, 3-furyle, 2-pyridyle, 4-pyridyle et 2-benzofuryle. Dans la formule générale (I), 'R2' et 'R3' sont choisis séparément parmi hétéroaryle, cycloalkyle et aryle, les radicaux hétéroaryle, cycloalkyle et aryle étant substitués à des positions admettant la substitution par un ou plusieurs radicaux choisis parmi hydrido, halo, alkylthio inférieur, alkylsulfinyle inférieur, alkylsulfonyle inférieur, aminosulfonyle, alkyle inférieur, cyano, carboxyle, alcoxycarbonyle inférieur, haloalkyle inférieur, hydroxyle, alcoxy inférieur, hydroxyalkyle inférieur, alcoxyalkyle inférieur, haloalcoxy inférieur, amino, alkylamino inférieur, phénylamino et nitro. Dans la formule générale (I), 'R4' est choisi parmi hydrido, alkyle inférieur et acyle. L'invention concerne également des sels de ces composés de formule générale qui sont pharmaceutiquement acceptables.

  描述了一类用于治疗炎症和炎症相关疾病的化合物。特别感兴趣的化合物由式（I）定义，其中R1从较低的烷基，较低的卤代烷基，较低的羟基烷基，较低的氧烷基，较低的烯氧基烷基，巯基，较低的烷基羰基，较低的卤代烷基羰基，苯基羰基，较低的芳基烷基羰基，较低的芳基烯基，较低的芳氧基烷基，较低的芳基氧烷基，较低的芳基磺酰基，较低的芳基烷基磺酰基，较低的芳基硫代烷基，较低的杂环芳基烷基硫代烷基和杂环芳基，所述杂环芳基选择自2-噻吩基，2-呋喃基，3-呋喃基，2-吡啶基，4-吡啶基和2-苯并呋喃基；其中R2和R3分别选择自杂环芳基，环烷基和芳基，其中杂环芳基，环烷基和芳基基团在可取代位置上用一个或多个基团进行取代，所述基团选择自氢基，卤素基，较低的烷基硫基，较低的烷基亚砜基，较低的烷基磺酰基，氨基磺酰基，较低的烷基，氰基，羧基，较低的烷氧基羰基，较低的卤代烷基，羟基，较低的氧烷基，较低的羟基烷基，较低的氧烷基烷基，较低的卤代氧烷基，氨基，较低的烷基氨基，苯基氨基和硝基；其中R4选择自氢基，较低的烷基和酰基；或其药学上可接受的盐。
• 3,4-diaryl thiophenes and analogs thereof having use as anti-inflammatory agents
  申请人：G.D. Searle & Co.

  公开号：US20030013744A1

  公开（公告）日：2003-01-16

  A class of 3,4-diaryl substituted thiophene, furan and pyrrole derivatives and analogs thereof, pharmaceutical compositions containing them and methods of using them to treat inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I: 1 wherein Y is selected from O, S and NR 1 ; wherein R 1 is selected from hydrido and lower alkyl; wherein X is one or two substituent selected from hydrido, halo, lower alkoxycarbonyl and carboxyl; wherein R 2 and R 3 are independently aryl or heteroaryl; and wherein R 2 and R 3 are optionally substituted at a substitutable position with one or more radicals selected from sulfamyl, alkylsulfonyl, halo, lower alkoxy and lower alkyl; or a pharmaceutically-acceptable salt thereof.

  一类3,4-二芳基取代的噻吩、呋喃和吡咯衍生物及其类似物，包括含有它们的制药组合物和使用它们治疗炎症和炎症相关疾病的方法。特别感兴趣的化合物由公式I定义：其中Y选择自O、S和NR1；其中R1选择自氢和较低的烷基；其中X是一个或两个取代基，选择自氢、卤素、较低的烷氧羰基和羧基；其中R2和R3分别为芳基或杂芳基；其中R2和R3在可取代位置上可以选择一个或多个基团进行取代，选择自磺酰胺基、烷基磺酰基、卤素、较低的烷氧基和较低的烷基；或其药学上可接受的盐。