5-Methyl-2-(methylsulfonyl)-4-[4-(methylsulphonyl)phenyl]-6-(trifluoromethyl)pyrimidine | 477771-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-Methyl-2-(methylsulfonyl)-4-[4-(methylsulphonyl)phenyl]-6-(trifluoromethyl)pyrimidine
• 英文别名: 5-methyl-2-methylsulfonyl-4-(4-methylsulfonylphenyl)-6-(trifluoromethyl)pyrimidine
• CAS: 477771-05-4
• 化学式: C₁₄H₁₃F₃N₂O₄S₂
• 分子量: 394.395
• InChiKey: RAMJJORAFYQFIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-Methyl-2-(methylsulfonyl)-4-[4-(methylsulphonyl)phenyl]-6-(trifluoromethyl)pyrimidine 、 环己胺 以 乙腈 为溶剂， 生成 N-cyclohexyl-5-methyl-4-(4-(methylsulfonyl)phenyl)-6-(trifluoromethyl)pyrimidin-2-amine
  参考文献：
  名称：

  Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors

  摘要：

  A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4(methylsulfonyl) phenyl]-6-(trifluoromethyl) pyrimidine (47), a member of the 2- pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic pro. le, high brain penetration and good efficacy in rat models of hypersensitivity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.085
• 作为产物：
  描述：

  5-Methyl-2-(methylthio)-4-[4-(methylthio)phenyl]-6-(trifluoromethyl)pyrimidine 在 Oxone 作用下， 以 甲醇 、 水 为溶剂， 生成 5-Methyl-2-(methylsulfonyl)-4-[4-(methylsulphonyl)phenyl]-6-(trifluoromethyl)pyrimidine
  参考文献：
  名称：

  Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors

  摘要：

  A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4(methylsulfonyl) phenyl]-6-(trifluoromethyl) pyrimidine (47), a member of the 2- pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic pro. le, high brain penetration and good efficacy in rat models of hypersensitivity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.02.085

文献信息

• PYRIMIDINE DERIVATIVES
  申请人：Bravi Gianpaolo

  公开号：US20100267755A1

  公开（公告）日：2010-10-21

  The invention provides the compounds of formula (I) and pharmaceutically acceptable salts thereof, in which: R 1 and R 2 are independently selected from the group consisting of H, C 1-6 alkyl, C 1-2 alkyl substituted by one to five fluorine atoms, C 3-6 alkenyl, C 3-6 alkynyl, C 3-10 cycloalkylC 0-6 alkyl, C 4-12 bridged cycloalkyl, A(CR 7 R 8 ) n and B(CR 7 R 8 ) n ; R 3 is selected from the group consisting of C 1-6 alkyl, NH 2 and R 10 CONH; R 4 is C 1-2 alkyl substituted by one to five fluorine atoms; R 5 is selected from the group consisting of H, C 1-4 alkyl, C 1-2 alkyl substituted with one to five fluorine atoms, halogen and C 3-10 cycloalkylC 0-6 alkyl, with the proviso that when R 6 is H R 5 is not H. R 6 is selected from the group consisting of H, C 1-4 alkyl, C 1-2 alkyl substituted with one to five fluorine atoms, halogen, C 1-4 alkoxy, CN, NO 2 , C 1-6 alkylOCO, NH 2 CO, C 1-6 alkylNHCO, NH 2 , C 1-6 alkylNH, (C 1-6 alkyl) 2 N, (C 1-6 alkyl) 2 NCO, C 1-6 alkylCONH, NH 2 SO 2 , C 1-6 alkylNHSO 2 , (C 1-6 alkyl) 2 NSO 2 , C 1-6 alkylSO 2 NH, ArSO 2 NH, C 1-6 alkylSO 2 , ArSO 2 , C 3-10 cycloalkylC 0-6 alkyl, C 3-6 alkenyl and C 3-6 alkynyl, with the proviso that when R 5 is H R 6 is not H. R 7 and R 8 are independently selected from H or C 1-6 alkyl; A is an unsubstituted 5- or 6-membered heteroaryl or an unsubstituted 6-membered aryl, or a 5- or 6-membered heteroaryl or a 6-membered aryl substituted by one or more R 9 ; R 9 is selected from the group consisting of hydroxy, halogen, C 1-6 alkyl, C 1-6 alkyl substituted by one more fluorine atoms, C 1-6 alkoxy, C 1-6 alkoxy substituted by one or more F, NH 2 SO 2 and C 1-6 alkylSO 2 ; R 10 is selected from the group consisting of H, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylOC 1-6 alkyl, phenyl, HO 2 CC 1-6 alkyl, C 1-6 alkylOCOC 1-6 alkyl, C 1-6 alkylOCO, H 2 NC 1-6 alkyl, C 1-6 alkylOCONHC 1-6 alkyl and C 1-6 alkylCONHC 1-6 alkyl; B is selected from the group consisting of defines the point of attachment of the ring; and n is 0 to 4. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of pain, fever and inflammation of a variety of conditions and diseases.

  本发明提供了式（I）化合物及其药学上可接受的盐，其中：R1和R2独立地选自H，C1-6烷基，被一到五个氟原子取代的C1-2烷基，C3-6烯基，C3-6炔基，C3-10环烷基C0-6烷基，C4-12桥环烷基，A（CR7R8）n和B（CR7R8）n；R3选自C1-6烷基，NH2和R10CONH；R4是被一到五个氟原子取代的C1-2烷基；R5选自H，C1-4烷基，被一到五个氟原子取代的C1-2烷基，卤素和C3-10环烷基C0-6烷基，但当R6为H时，R5不为H；R6选自H，C1-4烷基，被一到五个氟原子取代的C1-2烷基，卤素，C1-4烷氧基，CN，NO2，C1-6烷基羧酰基，NH2CO，C1-6烷基氨基酰基，NH2，C1-6烷基氨基，（C1-6烷基）2N，（C1-6烷基）2NCO，C1-6烷基酰胺基，NH2SO2，C1-6烷基NHSO2，（C1-6烷基）2NSO2，C1-6烷基SO2NH，ArSO2NH，C1-6烷基SO2，ArSO2，C3-10环烷基C0-6烷基，C3-6烯基和C3-6炔基，但当R5为H时，R6不为H；R7和R8独立地选自H或C1-6烷基；A是未取代的5-或6-成员杂芳基或未取代的6-成员芳基，或被一个或多个R9取代的5-或6-成员杂芳基或6-成员芳基；R9选自羟基，卤素，C1-6烷基，被一个或多个氟原子取代的C1-6烷基，C1-6烷氧基，被一个或多个F取代的C1-6烷氧基，NH2SO2和C1-6烷基SO2；R10选自H，C1-6烷基，C1-6烷氧基，C1-6烷基氧基C1-6烷基，苯基，HO2CC1-6烷基，C1-6烷氧基COC1-6烷基，C1-6烷氧基CO，H2NC1-6烷基，C1-6烷氧基CONHC1-6烷基和C1-6烷基CONHC1-6烷基；B选自定义环的连接点；n为0到4。式（I）化合物是COX-2的有效和选择性抑制剂，并可用于治疗各种疾病和病症的疼痛、发热和炎症。
• [EN] PYRIMIDINE DERIVATIVES<br/>[FR] DERIVES DE PYRIMIDINE
  申请人：GLAXO GROUP LTD

  公开号：WO2002096886A1

  公开（公告）日：2002-12-05

  The invention provides the compounds of formula (I) and pharmaceutically acceptable salts thereof, in which: R?1 and R2¿ are independently selected from the group consisting of H, C¿1-6?alkyl, C1-2alkyl substituted by one to five fluorine atoms, C3-6alkenyl, C3-6alkynyl, C3-cycloalkylC0-6alkyl, C4-12bridged cycloalkyl, A(CR?7R8)¿n and B(CR7R8)n; R3 is selected from the group consisting of C¿1-6?alkyl, NH2 and R?10CONH; R4¿ is C¿1-2?alkyl substituted by one to five fluorine atoms; R?5¿ is selected from the group consisting of H, C¿1-4?alkyl, C1-2alkyl substituted with one to five fluorine atoms, halogen and C3-10¿cycloalkylC?0-6alkyl, with the proviso that when R?6 is H R5¿ is not H. R6 is selected from the group consisting of H, C¿1-4?alkyl, C1-2alkyl substituted with one to five fluorine atoms, halogen, C1-4alkoxy, CN, NO2, C1-6alkylOCO, NH2CO C1-6alkylNHCO, NH2, C1-6alkylNH, (C1-6alkyl)2N, (C1-6alkyl)2NCO, C1-6alkylCONH, NH2SO2, C1-6alkylNHSO2 (C1-6alkyl)2NSO2, C1-6alkylSO2NH, ArSO2NH, C1-6alkylSO2, ArSO2, C¿3-10cycloalkylC?0-6alkyl, C3-6alkenyl and C3-6alkynyl, with the proviso that when R?5 is H R6¿ is not H. R?7 and R8¿ are independently selected from H or C¿1-6?alkyl; A is an unsubstituted 5- or 6-membered heteroaryl or an unsubstituted 6-membered aryl, or a 5- or 6-membered heteroaryl or a 6-membered aryl substituted by one or more R?9¿ is selected from the group consisting of hydroxy, halogen, C¿1-6?alkyl, C1-6alkyl substituted by one mor fluorine atoms, C1-6alkoxy, C1-6alkoxy substituted by one or more F, NH2SO2 and C1-6alkylSO2; R?10¿ is selected from the group consisting of H, C¿1-6?alkyl, C1-6alkoxy, C1-6alkylOC1-6alkyl, phenyl, HO2CC1-6alkyl, C1-6alkylOCOC1-6alkyl, C1-6alkylOCO, H2NC1-6alkyl, C1-6alkylOCONHC1-6alkyl and C1-6alkylCONHC1-6alkyl; B is selected from the group consisting of (II) and (III)where (IV) defines the point of attachmnent of the ring; and n is 0 to 4. Compounds of formula (I) are potent and selective inhibitors of COX-2 and are of use in the treatment of pain, fever and inflammation of a variety of conditions and diseases.
• Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors
  作者：Martin E. Swarbrick、Paul J. Beswick、Robert J. Gleave、Richard H. Green、Sharon Bingham、Chas Bountra、Malcolm C. Carter、Laura J. Chambers、Iain P. Chessell、Nick M. Clayton、Sue D. Collins、John A. Corfield、C. David Hartley、Savvas Kleanthous、Paul F. Lambeth、Fiona S. Lucas、Neil Mathews、Alan Naylor、Lee W. Page、Jeremy J. Payne、Neil A. Pegg、Helen S. Price、John Skidmore、Alexander J. Stevens、Richard Stocker、Sharon C. Stratton、Alastair J. Stuart、Joanne O. Wiseman

  DOI：10.1016/j.bmcl.2009.02.085

  日期：2009.8

  A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4(methylsulfonyl) phenyl]-6-(trifluoromethyl) pyrimidine (47), a member of the 2- pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic pro. le, high brain penetration and good efficacy in rat models of hypersensitivity. (C) 2009 Elsevier Ltd. All rights reserved.