5-Methyl-2-(methylthio)-4-[4-(methylthio)phenyl]-6-(trifluoromethyl)pyrimidine | 477771-04-3

• 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-(methylthio)-4-[4-(methylthio)phenyl]-6-(trifluoromethyl)pyrimidine
• 英文别名: 5-methyl-2-methylsulfanyl-4-(4-methylsulfanylphenyl)-6-(trifluoromethyl)pyrimidine
• CAS: 477771-04-3
• 化学式: C₁₄H₁₃F₃N₂S₂
• 分子量: 330.398
• InChiKey: SVPJBACKKWIASE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 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：
  76.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  4,4,4-Trifluoro-2-methyl-1-[4-(methylthio)phenyl]butane-1,3-dione 、 2-甲基-2-疏基硫酸脲 以 乙腈 为溶剂， 生成 5-Methyl-2-(methylthio)-4-[4-(methylthio)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.