5-Amino-6-(2,4-difluoro-phenylamino)-indan-1-one | 1027581-50-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5-Amino-6-(2,4-difluoro-phenylamino)-indan-1-one
• 英文别名: 5-Amino-6-(2,4-difluoroanilino)-2,3-dihydroinden-1-one
• CAS: 1027581-50-5
• 化学式: C₁₅H₁₂F₂N₂O
• 分子量: 274.27
• InChiKey: CEIUSKKWKMVSOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-Amino-6-(2,4-difluoro-phenylamino)-indan-1-one 在 sodium hydroxide 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 N-[6-(2,4-Difluoro-phenylamino)-1-oxo-indan-5-yl]-methanesulfonamide
  参考文献：
  名称：

  Cyclooxygenase-2 Inhibitors. Synthesis and Pharmacological Activities of 5-Methanesulfonamido-1-indanone Derivatives

  摘要：

  The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing nonsteroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)thio]-5-methanesulfonamido-1-indanone (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted B-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t(1/2) in squirrel monkeys, and seems less ulcergenic than 2 in rats.

  DOI：

  10.1021/jm00025a007
• 作为产物：
  描述：

  5-氨基茚旦 在 吡啶 、 chromium(VI) oxide 、 盐酸 、 氢氧化钾 、 tetrafluoroboric acid 、 三氟甲磺酸三甲基硅酯 、 溴 、 铁粉 、 铜 、 氯化铵 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.5h， 生成 5-Amino-6-(2,4-difluoro-phenylamino)-indan-1-one
  参考文献：
  名称：

  Cyclooxygenase-2 Inhibitors. Synthesis and Pharmacological Activities of 5-Methanesulfonamido-1-indanone Derivatives

  摘要：

  The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing nonsteroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)thio]-5-methanesulfonamido-1-indanone (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted B-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t(1/2) in squirrel monkeys, and seems less ulcergenic than 2 in rats.

  DOI：

  10.1021/jm00025a007

文献信息

• Cyclooxygenase-2 Inhibitors. Synthesis and Pharmacological Activities of 5-Methanesulfonamido-1-indanone Derivatives
  作者：Chun-Sing Li、W. Cameron Black、Chi-Chung Chan、Anthony W. Ford-Hutchinson、Jacques-Yves Gauthier、Robert Gordon、Daniel Guay、Stacia Kargman、Cheuk K. Lau

  DOI：10.1021/jm00025a007

  日期：1995.12

  The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing nonsteroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)thio]-5-methanesulfonamido-1-indanone (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted B-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t(1/2) in squirrel monkeys, and seems less ulcergenic than 2 in rats.