2-(4-((2-propyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl)benzoic acid | 1432597-01-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-(4-((2-propyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl)benzoic acid
• 英文别名: 2-[4-[(5-Nitro-2-propylbenzimidazol-1-yl)methyl]indol-1-yl]benzoic acid；2-[4-[(5-nitro-2-propylbenzimidazol-1-yl)methyl]indol-1-yl]benzoic acid
• CAS: 1432597-01-7
• 化学式: C₂₆H₂₂N₄O₄
• 分子量: 454.485
• InChiKey: AIUSSFIJFZMNEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-propyl-5-nitro-1H-benzo[d]imidazole 在 potassium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 48.0h， 生成 2-(4-((2-propyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl)benzoic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluation of new 5-nitro benzimidazole derivatives as AT1 antagonists with anti-hypertension activities

  摘要：

  The design, synthesis, in vitro and in vivo evaluation of 5-nitro benzimidazole with 1,4-disubsituted or 1,5-disubsituted indole derivatives as novel angiotensin II receptor antagonist is outlined. Radioligand binding assays showed that 2-(4-((2-butyl-5-nitro-1H-benzo[d] imidazol-1-yl) methyl)-1H-indol-1-yl) benzoic acid, compound 3, displayed a high affinity for the angiotensin II type 1 receptor with IC50 value of 1.03 +/- 0.26 nM. The biological evaluation on spontaneously hypertensive rats and renal hypertensive rats showed that 3 could cause significant decrease on MBP in a dose dependent manner, whose maximal response lowered 30 mmHg of MBP at 5 mg/kg and 41 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, which is better than Losartan. Taken together 3 could be considered as an effective and durable anti-hypertension drug candidate. These encouraging results are deserved of further investigation towards its use for therapeutic benefit. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.008

文献信息

• Synthesis, Anti-hypertensive Effect of a Novel Angiotensin II AT1 Receptor Antagonist and its Anti-tumor Activity in Prostate Cancer
  作者：Y.-J. Da、W.-D. Yuan、L.-F. Zhu、Z.-L. Chen

  DOI：10.1055/s-0032-1329952

  日期：——

  Since the first non-peptide Ang II receptor antagonist was originally reported, it has become the most common target in the development of new treatments for hypertension. In recent years, all components of the classical RAS have been reported in the prostate, these results suggest the possibility that ARB is a novel therapeutic class of agents for prostate cancer. In this study, a new compound 2-(4-((2-propyl-5-nitro-1H-benzo[d]imidazol-1-yl) methyl)-1H-indol-1-yl) benzoic acid was synthesized and evaluated as a novel angiotensin II AT(1) receptor antagonist by radioligand binding assays, anti-hypertensive assays in vivo and oral acute toxicity test. MTT assays and tests in nude mice were used to demonstrate its anti-tumor activity. This new compound showed high affinity to AT(1) receptor and anti-hypertensive activity in spontaneously hypertensive rats and renal hypertensive rats. Moreover, in human prostate cancer cells and in athymic nude mice bearing human prostate cancer cells, we observed this new compound had an efficient antiproliferative activity in vitro and anti-tumor activity in vivo. The preliminary pharmacological characteristics with oral acute toxicity test suggested that this new compound can be considered as a candidate for both anti-hypertensive and antitumor drug.
• Design, synthesis and biological evaluation of new 5-nitro benzimidazole derivatives as AT1 antagonists with anti-hypertension activities
  作者：Weibo Zhu、Yajing Da、Dan Wu、Huiling Zheng、Linfeng Zhu、Li Wang、Yijia Yan、Zhilong Chen

  DOI：10.1016/j.bmc.2014.02.008

  日期：2014.4

  The design, synthesis, in vitro and in vivo evaluation of 5-nitro benzimidazole with 1,4-disubsituted or 1,5-disubsituted indole derivatives as novel angiotensin II receptor antagonist is outlined. Radioligand binding assays showed that 2-(4-((2-butyl-5-nitro-1H-benzo[d] imidazol-1-yl) methyl)-1H-indol-1-yl) benzoic acid, compound 3, displayed a high affinity for the angiotensin II type 1 receptor with IC50 value of 1.03 +/- 0.26 nM. The biological evaluation on spontaneously hypertensive rats and renal hypertensive rats showed that 3 could cause significant decrease on MBP in a dose dependent manner, whose maximal response lowered 30 mmHg of MBP at 5 mg/kg and 41 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, which is better than Losartan. Taken together 3 could be considered as an effective and durable anti-hypertension drug candidate. These encouraging results are deserved of further investigation towards its use for therapeutic benefit. (c) 2014 Elsevier Ltd. All rights reserved.