4-cyclohexyl-5-(3-fluorophenyl)-2-ethyloxazole | 415679-10-6

• 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-cyclohexyl-5-(3-fluorophenyl)-2-ethyloxazole
• 英文别名: 4-Cyclohexyl-2-ethyl-5-(3-fluorophenyl)-1,3-oxazole
• CAS: 415679-10-6
• 化学式: C₁₇H₂₀FNO
• 分子量: 273.35
• InChiKey: RSXGMROTCLLCIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  26
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-cyclohexyl-5-(3-fluorophenyl)-2-ethyloxazole 在 氯磺酸 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 3.0h， 生成 4-(4-Cyclohexyl-2-ethyl-oxazol-5-yl)-2-fluoro-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：

  2-cyclohexyl-1-(3-fluorophenyl)-2-oxoethyl propionate 在 ammonium acetate 、 溶剂黄146 作用下， 生成 4-cyclohexyl-5-(3-fluorophenyl)-2-ethyloxazole
  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

• TRICYCLIC INHIBITORS OF HYDROXYSTEROID DEHYDROGENASES
  申请人：Powers Jay P.

  公开号：US20100280073A1

  公开（公告）日：2010-11-04

  The present invention provides tricyclic compounds according to formula (I): (I) where R 1 , R 2 , R 3 , W, X, Y, Z, m, n, and p are as defined in the description; as well as pharmaceutical compositions comprising the same, methods of use of the compounds and compositions of the invention for the treatment of conditions associated with hydroxysteroid dehydrogenases (e.g., 11-HSD1), and the use of the compounds of the invention in the preparation of medicaments for the treatment of hydroxysteroid dehydrogenase-associated conditions.

  本发明提供了公式（I）所示的三环化合物：（I）其中R1，R2，R3，W，X，Y，Z，m，n和p如描述中所定义的；以及包含相同化合物的药物组合物，使用本发明的化合物和组合物治疗与羟基类固醇脱氢酶（例如11-HSD1）相关的疾病的方法，以及使用本发明的化合物制备治疗羟基类固醇脱氢酶相关疾病的药物。
• US8765788B2
  申请人：——

  公开号：US8765788B2

  公开（公告）日：2014-07-01
• 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
  作者：Hiromasa Hashimoto、Katsuaki Imamura、Jun-ichi Haruta、Korekiyo Wakitani

  DOI：10.1021/jm010484p

  日期：2002.3.1

  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.