7-bromo-2-(2-chlorophenyl)imidazo[4,5-c]quinolin-4(5H)-one | 1355478-26-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-bromo-2-(2-chlorophenyl)imidazo[4,5-c]quinolin-4(5H)-one
• 英文别名: 7-Bromo-2-(2-chlorophenyl)-3,5-dihydroimidazo[4,5-c]quinolin-4-one
• CAS: 1355478-26-0
• 化学式: C₁₆H₉BrClN₃O
• 分子量: 374.624
• InChiKey: WTAIERVWPQNXDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-bromo-2-(2-chlorophenyl)imidazo[4,5-c]quinolin-4(5H)-one 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.5h， 生成 7-Bromo-2-(2-chlorophenyl)-3,5-dimethylimidazo[4,5-c]quinolin-4-one
  参考文献：
  名称：

  Synthesis and biological evaluation of substituted imidazoquinoline derivatives as mPGES-1 inhibitors

  摘要：

  We have Previously reported 7-bromo-2-(2-chrolophenyl)-imidazoquinolin-4(5H)-one (1) as a novel potent mPGES-1 inhibitor. To clarify the essential functional groups of 1 for inhibition of mPGES-1, we investigated this compound structure-activity relationship following substitution at the C(4)-position and N-alkylation at the N(1)-, the N(3)-, and the N(5)-positions of I. To prepare the target compounds, we established a good methodology for selective N-alkylation of the imidazoquinolin-4-one, that is, selective alkylation of 1 at the N(3)- and N(5)-positions was achieved by use of an appropriate base and introduction of a protecting group at the nitrogen atom in the imidazole part, respectively. Replacement of the C(4)-oxo group with nitrogen- or sulfur- linked substituents gave decreased inhibitory activity for mPGES-1, and introduction of alkyl groups on the nitrogen atom at the N(1)-, the N(3)-, and the N(5)-positions resulted in even larger loss of inhibitory activity. These results revealed that the C(4)-oxo group, and the hydrogen atoms at the N(5)-position and the imidazole part were the best substituents. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.018
• 作为产物：
  描述：

  HCl 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 8.0h， 以89%的产率得到7-bromo-2-(2-chlorophenyl)imidazo[4,5-c]quinolin-4(5H)-one
  参考文献：
  名称：

  Synthesis and SAR study of imidazoquinolines as a novel structural class of microsomal prostaglandin E2 synthase-1 inhibitors

  摘要：

  The imidazoquinoline derivative 1 was found as a novel mPGES-1 inhibitor. Optimization of 1 led to the identification of the 2-chlorophenyl group at the C(2)-position and the quinolone structure at the C(4)-position. Compound 33, the most potent synthesized compound, showed excellent mPGES-1 inhibition (IC50 = 9.1 nM) with high selectivity (>1000-fold) over both COX-1 and COX-2. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.015

文献信息

• 7-Phenyl-imidazoquinolin-4(5H)-one derivatives as selective and orally available mPGES-1 inhibitors
  作者：Tomoya Shiro、Keisuke Kakiguchi、Hirotada Takahashi、Hidetaka Nagata、Masanori Tobe

  DOI：10.1016/j.bmc.2013.03.069

  日期：2013.6

  To identify compounds with strong mPGES-1 inhibitory activity and clear in vitro ADME profile, we optimized the lead compound 1 by carrying our substitutions at the C(7)-and C(8)-positions. Replacement of the bromine atom of 1 with various substituents led to identification of the phenyl group as the best C(7)-substituent giving strong inhibitory activity with good in vitro ADME profile. Further SAR examination on both the C(2)-and the C(7)-phenyl groups provided compound 39 as the best candidate for further development. Compound 39 exhibited strong mPGES-1 inhibitory activity (IC50 = 4.1 nM), potent cell-based functional activity (IC50 = 33 nM) with good mPGES-1 selectivity (over 700-fold), excellent in vitro ADME profile, and good oral absorption in rat PK study. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and SAR study of imidazoquinolines as a novel structural class of microsomal prostaglandin E2 synthase-1 inhibitors
  作者：Tomoya Shiro、Hirotada Takahashi、Keisuke Kakiguchi、Yoshifumi Inoue、Keiki Masuda、Hidetaka Nagata、Masanori Tobe

  DOI：10.1016/j.bmcl.2011.11.015

  日期：2012.1

  The imidazoquinoline derivative 1 was found as a novel mPGES-1 inhibitor. Optimization of 1 led to the identification of the 2-chlorophenyl group at the C(2)-position and the quinolone structure at the C(4)-position. Compound 33, the most potent synthesized compound, showed excellent mPGES-1 inhibition (IC50 = 9.1 nM) with high selectivity (>1000-fold) over both COX-1 and COX-2. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of substituted imidazoquinoline derivatives as mPGES-1 inhibitors
  作者：Tomoya Shiro、Keisuke Kakiguchi、Hirotada Takahashi、Hidetaka Nagata、Masanori Tobe

  DOI：10.1016/j.bmc.2013.01.018

  日期：2013.4

  We have Previously reported 7-bromo-2-(2-chrolophenyl)-imidazoquinolin-4(5H)-one (1) as a novel potent mPGES-1 inhibitor. To clarify the essential functional groups of 1 for inhibition of mPGES-1, we investigated this compound structure-activity relationship following substitution at the C(4)-position and N-alkylation at the N(1)-, the N(3)-, and the N(5)-positions of I. To prepare the target compounds, we established a good methodology for selective N-alkylation of the imidazoquinolin-4-one, that is, selective alkylation of 1 at the N(3)- and N(5)-positions was achieved by use of an appropriate base and introduction of a protecting group at the nitrogen atom in the imidazole part, respectively. Replacement of the C(4)-oxo group with nitrogen- or sulfur- linked substituents gave decreased inhibitory activity for mPGES-1, and introduction of alkyl groups on the nitrogen atom at the N(1)-, the N(3)-, and the N(5)-positions resulted in even larger loss of inhibitory activity. These results revealed that the C(4)-oxo group, and the hydrogen atoms at the N(5)-position and the imidazole part were the best substituents. (C) 2013 Elsevier Ltd. All rights reserved.