4-(4-Fluoro-phenyl)-5-(3-fluoro-phenyl)-2-methyl-oxazole | 180200-81-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-Fluoro-phenyl)-5-(3-fluoro-phenyl)-2-methyl-oxazole
• 英文别名: 5-(3-Fluorophenyl)-4-(4-fluorophenyl)-2-methyl-1,3-oxazole
• CAS: 180200-81-1
• 化学式: C₁₆H₁₁F₂NO
• 分子量: 271.266
• InChiKey: BGWSRGLMQXGKRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  26
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-Fluoro-phenyl)-5-(3-fluoro-phenyl)-2-methyl-oxazole 在 氯磺酸 作用下， 以 氯仿 为溶剂， 反应 3.0h， 生成 2-Fluoro-4-[4-(4-fluoro-phenyl)-2-methyl-oxazol-5-yl]-benzenesulfonyl chloride
  参考文献：
  名称：

  4-(4-Cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as Selective Cyclooxygenase-2 Inhibitors:  Enhancement of the Selectivity by Introduction of a Fluorine Atom and Identification of a Potent, Highly Selective, and Orally Active COX-2 Inhibitor JTE-522

  摘要：

  A series of 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamide derivatives were synthesized and evaluated for their abilities to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) enzymes. In this series, substituent effects at the ortho position to the sulfonamide group on the phenyl ring were examined. Most substituents reduced or lost both COX-2 and COX-1 activities. In contrast, introduction of a fluorine atom preserved COX-2 potency and notably increased COX-1/COX-2 selectivity. This work led to the identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522 [9d, 4-(4-cyclohexyl-2-methyloxazol-5-yl)2-fluorobenzenesulfonamide], which is currently in phase II clinical trials for the treatment of rheumatoid arthritis, osteoarthritis, and acute pain.

  DOI：

  10.1021/jm010484p
• 作为产物：
  描述：

  [1-(3-Fluorophenyl)-2-(4-fluorophenyl)-2-oxoethyl] acetate 在 ammonium acetate 、 溶剂黄146 作用下， 反应 5.0h， 生成 4-(4-Fluoro-phenyl)-5-(3-fluoro-phenyl)-2-methyl-oxazole
  参考文献：
  名称：

  4-(4-Cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as Selective Cyclooxygenase-2 Inhibitors:  Enhancement of the Selectivity by Introduction of a Fluorine Atom and Identification of a Potent, Highly Selective, and Orally Active COX-2 Inhibitor JTE-522

  摘要：

  A series of 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamide derivatives were synthesized and evaluated for their abilities to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) enzymes. In this series, substituent effects at the ortho position to the sulfonamide group on the phenyl ring were examined. Most substituents reduced or lost both COX-2 and COX-1 activities. In contrast, introduction of a fluorine atom preserved COX-2 potency and notably increased COX-1/COX-2 selectivity. This work led to the identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522 [9d, 4-(4-cyclohexyl-2-methyloxazol-5-yl)2-fluorobenzenesulfonamide], which is currently in phase II clinical trials for the treatment of rheumatoid arthritis, osteoarthritis, and acute pain.

  DOI：

  10.1021/jm010484p

文献信息

• Heterocyclic aromatic oxazole compounds and use thereof
  申请人：——

  公开号：US20020198244A1

  公开（公告）日：2002-12-26

  A heterocyclic aromatic oxazole compound of the formula (I) 1 wherein Z is an oxygen atom; one of R and R 1 is a group of the formula 2 wherein R 3 is lower alkyl, amino or lower alkylamino, and R 4 , R 5 , R 6 and R 7 are the same or different and each is hydrogen atom, halogen atom, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy or amino, provided that at least one of R 4 , R 5 , R 6 and R 7 is not hydrogen atom, and the other is an optionally substituted cycloalkyl, an optionally substituted heterocyclic group or an optionally substituted aryl; and R 2 is a lower alkyl or a halogenated lower alkyl, and a pharmaceutically acceptable salt thereof. The heterocyclic aromatic oxazole compound and pharmaceutically acceptable salts thereof have antipyretic action, analgesic action, anti-inflammatory action, and particularly, selective inhibitory action on cyclooxygenase-2 (COX-2), and are expected to be useful as anti-inflammatory agents with less side-effects such as digestive tract disorders.

  式(I)中，Z为氧原子；R和R1中的一个为式2的基团，其中R3为低碳基、氨基或低碳基氨基，R4、R5、R6和R7相同或不同，且每个为氢原子、卤素原子、低碳基、低碳氧基、三氟甲基、羟基或氨基，但至少有一个为非氢原子，另一个为可选取代的环烷基、可选取代的杂环基或可选取代的芳基；R2为低碳基或卤代低碳基，以及其药学上可接受的盐。该杂环芳香族噁唑化合物及其药学上可接受的盐具有退热作用、镇痛作用、抗炎作用，特别是对环氧合酶-2 (COX-2)的选择性抑制作用，并有望作为抗炎剂使用，具有较少的消化道副作用。
• HETEROAROMATIC OXAZOLE COMPOUNDS AND USE THEREOF
  申请人：Japan Tobacco Inc.

  公开号：EP0745596A1

  公开（公告）日：1996-12-04

  A heterocyclic aromatic oxazole compound of the formula (I) wherein Z is an oxygen atom; one of R and R1 is a group of the formula wherein R3 is lower alkyl, amino or lower alkylamino, and R4, R5, R6 and R7 are the same or different and each is hydrogen atom, halogen atom, lower alkyl, lower alkoxy, trifluoromethyl, hydroxy or amino, provided that at least one of R4, R5, R6 and R7 is not hydrogen atom, and the other is an optionally substituted cycloalkyl, an optionally substituted heterocyclic group or an optionally substituted aryl; and R2 is a lower alkyl or a halogenated lower alkyl, and a pharmaceutically acceptable salt thereof. The heterocyclic aromatic oxazole compound and pharmaceutically acceptable salts thereof have antipyretic action, analgesic action, anti-inflammatory action, and particularly, selective inhibitory action on cyclooxygenase-2 (COX-2), and are expected to be useful as anti-inflammatory agents with less side-effects such as digestive tract disorders.

  式（I）的杂环芳香族噁唑化合物 其中 Z 是氧原子；R 和 R1 中的一个是式中的基团 其中 R3 是低级烷基、氨基或低级烷基氨基，R4、R5、R6 和 R7 相同或不同，且各自是氢原子、卤素原子、低级烷基、低级烷氧基、三氟甲基、羟基或氨基，条件是 R4、R5、R6 和 R7 中至少有一个不是氢原子，另一个是任选取代的环烷基、任选取代的杂环基团或任选取代的芳基；以及 R2 是低级烷基或卤代低级烷基，及其药学上可接受的盐。杂环芳香族噁唑化合物及其药学上可接受的盐具有解热作用、镇痛作用、抗炎作用，特别是对环氧化酶-2（COX-2）具有选择性抑制作用，可望作为副作用较少（如消化道功能紊乱）的抗炎药物。
• US5994381A
  申请人：——

  公开号：US5994381A

  公开（公告）日：1999-11-30
• US6362209B1
  申请人：——

  公开号：US6362209B1

  公开（公告）日：2002-03-26