1-benzoyl-3-[(4-fluorophenylimino)methyl]indole | 1365974-57-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-benzoyl-3-[(4-fluorophenylimino)methyl]indole
• 英文别名: [3-[(4-Fluorophenyl)iminomethyl]indol-1-yl]-phenylmethanone
• CAS: 1365974-57-7
• 化学式: C₂₂H₁₅FN₂O
• 分子量: 342.372
• InChiKey: CCRRXQOCINWOLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯甲酰氯 在 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 1.16h， 生成 1-benzoyl-3-[(4-fluorophenylimino)methyl]indole
  参考文献：
  名称：

  N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: Synthesis and biological evaluation

  摘要：

  A group of N-1 and C-3 disubstituted-indole Schiff bases bearing an indole N-1 (R' = H, CH2Ph, COPh) substituent in conjunction with a C-3-CH=N-C6H4-4-X (X = F, Me, CF3, Cl) substituent were synthesized and evaluated as inhibitors of cyclooxygenase (COX) isozymes (COX-1/COX-2). Within this group of Schiff bases, compounds 15 (R-1 = CH2Ph, X = F), 17 (R-1 = CH2Ph, X = CF3), 18 (R-1 = COPh, X = F) and 20 (R-1 = COPh, X = CF3) were identified as effective and selective COX-2 inhibitors (COX-2 IC50's = 0.32-0.84 mu M range; COX-2 selectivity index (SI) = 113 to > 312 range). 1-Benzoyl-3-[(4-trifluoromethylphenylimino) methyl]indole (20) emerged as the most potent (COX-1 IC50 > 100 mu M; COX-2 IC50 = 0.32 mu M) and selective (SI >312) COX-2 inhibitor. Furthermore, compound 20 is a selective COX-2 inhibitor in contrast to the reference drug indomethacin that is a potent and selective COX-1 inhibitor (COX-1 IC50 = 0.13 mu M; COX-2 IC50 = 6.9 mu M, COX-2 SI = 0.02). Molecular modeling studies employing compound 20 showed that the phenyl CF3 substituent attached to the C=N spacer is positioned near the secondary pocket of the COX-2 active site, the C=N nitrogen atom is hydrogen bonded (N center dot center dot center dot NH = 2.85 angstrom) to the H90 residue, and the indole N-1 benzoyl is positioned in a hydrophobic pocket of the COX-2 active site near W387. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.130

文献信息

• N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: Synthesis and biological evaluation
  作者：Jatinder Kaur、Atul Bhardwaj、Zhangjian Huang、Edward E. Knaus

  DOI：10.1016/j.bmcl.2012.01.130

  日期：2012.3

  A group of N-1 and C-3 disubstituted-indole Schiff bases bearing an indole N-1 (R' = H, CH2Ph, COPh) substituent in conjunction with a C-3-CH=N-C6H4-4-X (X = F, Me, CF3, Cl) substituent were synthesized and evaluated as inhibitors of cyclooxygenase (COX) isozymes (COX-1/COX-2). Within this group of Schiff bases, compounds 15 (R-1 = CH2Ph, X = F), 17 (R-1 = CH2Ph, X = CF3), 18 (R-1 = COPh, X = F) and 20 (R-1 = COPh, X = CF3) were identified as effective and selective COX-2 inhibitors (COX-2 IC50's = 0.32-0.84 mu M range; COX-2 selectivity index (SI) = 113 to > 312 range). 1-Benzoyl-3-[(4-trifluoromethylphenylimino) methyl]indole (20) emerged as the most potent (COX-1 IC50 > 100 mu M; COX-2 IC50 = 0.32 mu M) and selective (SI >312) COX-2 inhibitor. Furthermore, compound 20 is a selective COX-2 inhibitor in contrast to the reference drug indomethacin that is a potent and selective COX-1 inhibitor (COX-1 IC50 = 0.13 mu M; COX-2 IC50 = 6.9 mu M, COX-2 SI = 0.02). Molecular modeling studies employing compound 20 showed that the phenyl CF3 substituent attached to the C=N spacer is positioned near the secondary pocket of the COX-2 active site, the C=N nitrogen atom is hydrogen bonded (N center dot center dot center dot NH = 2.85 angstrom) to the H90 residue, and the indole N-1 benzoyl is positioned in a hydrophobic pocket of the COX-2 active site near W387. (C) 2012 Elsevier Ltd. All rights reserved.