5-(4-chlorosulfonyl-3-fluorophenyl)-4-cyclohexyl-2-methyloxazole | 180200-79-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-chlorosulfonyl-3-fluorophenyl)-4-cyclohexyl-2-methyloxazole
• 英文别名: 4-(4-Cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonyl chloride；4-(4-cyclohexyl-2-methyl-1,3-oxazol-5-yl)-2-fluorobenzenesulfonyl chloride
• CAS: 180200-79-7
• 化学式: C₁₆H₁₇ClFNO₃S
• 分子量: 357.833
• InChiKey: RSOKIXUJSWCNSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4-chlorosulfonyl-3-fluorophenyl)-4-cyclohexyl-2-methyloxazole 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 2-benzyloxy-4-(4-cyclohexyl-2-methyloxazol-5-yl)benzenesulfonamide
  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：

  4-cyclohexyl-5-(3-fluorophenyl)-2-methyloxazole 在 氯磺酸 作用下， 以 氯仿 为溶剂， 反应 3.0h， 生成 5-(4-chlorosulfonyl-3-fluorophenyl)-4-cyclohexyl-2-methyloxazole
  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

• Process for producing oxazole compound
  申请人：Japan Tobacco Inc.

  公开号：US06372915B1

  公开（公告）日：2002-04-16

  The present invention relates to a method for producing a compound of the formula [7] wherein R1 is an optionally substituted cycloalkyl group, an optionally substituted aryl group or an optionally substituted heterocyclic group, R2 is a lower alkyl or a halogenated lower alkyl and R3 is a halogen atom or a hydrogen atom. The method of the present invention includes reacting compound [1] with thionyl chloride to give compound [2] and obtaining the objective compound [7] at a high yield via intermediate [5], and is utilizable for industrial production.

  本发明涉及一种制备式（7）化合物的方法，其中R1是可选取的取代环烷基、可选取的取代芳基或可选取的取代杂环基，R2是低碳基或卤代低碳基，R3是卤素原子或氢原子。本发明的方法包括将化合物（1）与氯化硫酰反应得到化合物（2），通过中间体（5）高产率地得到目标化合物（7），可用于工业生产。
• PROCESS FOR PRODUCING OXAZOLE COMPOUND
  申请人：Japan Tobacco Inc.

  公开号：EP1110955A1

  公开（公告）日：2001-06-27

  The present invention relates to a method for producing a compound of the formula [7] wherein R1 is an optionally substituted cycloalkyl group, an optionally substituted aryl group or an optionally substituted heterocyclic group, R2 is a lower alkyl or a halogenated lower alkyl and R3 is a halogen atom or a hydrogen atom. The method of the present invention includes reacting compound [1] with thionyl chloride to give compound [2] and obtaining the objective compound [7] at a high yield via intermediate [5], and is utilizable for industrial production.

  本发明涉及一种生产式[7]化合物的方法 其中R1是任选取代的环烷基、任选取代的芳基或任选取代的杂环基，R2是低级烷基或卤代低级烷基，R3是卤原子或氢原子。本发明的方法包括使化合物[1]与亚硫酰氯反应得到化合物[2]，并通过中间体[5]高产率地得到目的化合物[7]，可用于工业生产。
• Process for producing acetophenone compound
  申请人：Japan Tobacco Inc.

  公开号：US20020072613A1

  公开（公告）日：2002-06-13

  The present invention relates to a method for producing a compound of the formula [7] 1 wherein R 1 is an optionally substituted cycloalkyl group, an optionally substituted aryl group or an optionally substituted heterocyclic group, R 2 is a lower alkyl or a halogenated lower alkyl and R 3 is a halogen atom or a hydrogen atom. The method of the present invention includes reacting compound [1] with thionyl chloride to give compound [2] and obtaining the objective compound [7] at a high yield via intermediate [5], and is utilizable for industrial production. 2

  本发明涉及一种生产式[7&rsqb化合物的方法； 1 其中 R 1 是任选取代的环烷基、任选取代的芳基或任选取代的杂环基，R 2 是低级烷基或卤代低级烷基，R 3 是卤素原子或氢原子。本发明的方法包括将化合物[1]与亚硫酰氯反应，得到化合物[2]，并通过中间体[5]以高收率得到目的化合物[7]，并可用于工业生产。 2
• J. Med. Chem. 2002, 45, 1511-1517
  作者：

  DOI：——

  日期：——
• US6372915B1
  申请人：——

  公开号：US6372915B1

  公开（公告）日：2002-04-16