4-(5-(benzo[c][1,2,5]thiadiazol-5-ylmethoxy)-2-cyanophenoxy)-4-phenylbutanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻二唑类
• 英文名称: 4-(5-(benzo[c][1,2,5]thiadiazol-5-ylmethoxy)-2-cyanophenoxy)-4-phenylbutanoic acid
• 英文别名: 4-[5-(2,1,3-Benzothiadiazol-5-ylmethoxy)-2-cyanophenoxy]-4-phenylbutanoic acid；4-[5-(2,1,3-benzothiadiazol-5-ylmethoxy)-2-cyanophenoxy]-4-phenylbutanoic acid
• 化学式: C₂₄H₁₉N₃O₄S
• 分子量: 445.499
• InChiKey: BRNLOCVNSLNZBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-甲基乙酰苯胺 在 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 sodium dithionite 、 硫酸 、 四丁基溴化铵 、 水 、 硝酸 、 potassium carbonate 、 三乙胺 、 potassium iodide 、 potassium hydroxide 、 sodium hydroxide 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 苯 为溶剂， 反应 57.5h， 生成 4-(5-(benzo[c][1,2,5]thiadiazol-5-ylmethoxy)-2-cyanophenoxy)-4-phenylbutanoic acid
  参考文献：
  名称：

  Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists with antihypertensive activity

  摘要：

  A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. Preliminary screening results showed that 6e and 6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compound BQ123. The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that 6e was a selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.003

文献信息

• Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists with antihypertensive activity
  作者：Jin Cai、Ligang Liu、Kwon Ho Hong、Peng Wang、Lushen Li、Meng Cao、Chunlong Sun、Xiaoqing Wu、Xi Zong、Junqing Chen、Min Ji

  DOI：10.1016/j.bmc.2015.01.003

  日期：2015.2

  A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. Preliminary screening results showed that 6e and 6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compound BQ123. The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that 6e was a selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases. (c) 2015 Elsevier Ltd. All rights reserved.