4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazole-5-yl))biphenyl-4-yl]methyl]-imidazole-5-carboxylate | 154749-89-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazole-5-yl))biphenyl-4-yl]methyl]-imidazole-5-carboxylate
• 英文别名: 4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5-carboxylic acid；5-ethyl-2-propyl-3-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid
• CAS: 154749-89-0
• 化学式: C₄₂H₃₈N₆O₂
• 分子量: 658.803
• InChiKey: YBAWXMMHLYBCJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  50
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazole-5-yl))biphenyl-4-yl]methyl]-imidazole-5-carboxylate 在 盐酸 、 silica gel 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 生成 propyl 4-ethyl-2-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylate
  参考文献：
  名称：

  摘要：

  DMP 811 is a diacidic angiotensin II antagonist. It has relatively low oral bioavailability in rats. A prodrug approach to improving oral bioavailability was tested. Five esters were synthesized and their stability in rat plasma in vitro was determined. The hydrolysis rates of these five esters ranged from almost immediate to negligible. A simple n-propyl ester was hydrolyzed very slowly (<10% in 24 hr) in rat plasma in vitro, and after oral dosing in rats plasma prodrug concentrations were much greater than DMP 811 concentrations. A pivaloyloxymethyl ester (1) was hydrolyzed relatively rapidly in rat plasma in vitro. Prodrug 1 was rapidly hydrolyzed by the intestine in vitro, and the intestinal permeation of DMP 811 was increased. DMP 811 oral bioavailability was 47% in rats dosed with 10 mg/kg 1, compared to 11% for rats dosed with 10 mg/kg DMP 811. However, DMP 811 bioavailability was only 27% after a 2 mg/kg dose of 1. In vitro plasma hydrolysis of 1 was highly species-dependent, with a half-life of 13 hr in human plasma but only 1 min in rat plasma. The prodrug approach has potential for improving the oral bioavailability of DMP 811, but selection of the optimal prodrug must be done in humans or in a species, such as dogs, with hydrolysis characteristics closer to humans.

  DOI：

  10.1023/a:1016228129729
• 作为产物：
  描述：

  三苯基氯甲烷 、 5-乙基-2-丙基-3-[[4-[2-(2H-四唑-5-基)苯基]苯基]甲基]咪唑-4-羧酸 在 盐酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazole-5-yl))biphenyl-4-yl]methyl]-imidazole-5-carboxylate
  参考文献：
  名称：

  Prodrugs of imidazole carboxylic acids as angiotensin II receptor

  摘要：

  咪唑羧酸的前药是AII拮抗剂，对治疗高血压有用，公开了这些前药的药物组合物以及使用这些前药治疗高血压的方法。

  公开号：

  US05310929A1

文献信息

• Imidazole 5-position substituted angiotensin II antagonists
  申请人：The Du Pont Merck Pharmaceutical Company

  公开号：US05395844A1

  公开（公告）日：1995-03-07

  Novel substituted imidazoles of Formula (III), which are useful as angiotensin-II antagonists, are disclosed: ##STR1## These compounds, exemplified by the compound 1-((2'-((i-Amyloxycarbonylamino)sulfonyl)-3-fluoro-(1,1'-biphenyl)-4-yl)me thyl)-5-[2-(N-butyryl-N-pyridin-3-ylamino) ethylcarbonyl]-4-ethyl-2-propyl-1H-imidazole, are useful as antihypertensive agents.

  Formula (III)的新型取代咪唑，可用作抗肾素II拮抗剂，已被披露：##STR1## 这些化合物，例如化合物1-((2'-((i-氨氧羰基氨基)磺酰基)-3-氟-(1,1'-联苯)-4-基)甲基)-5-[2-(N-丁酰-N-吡啶-3-基氨基)乙酰基]-4-乙基-2-丙基-1H-咪唑，可用作降压药物。
• PRODRUGS OF IMIDAZOLE CARBOXYLIC ACIDS AS ANGIOTENSIN II RECEPTOR ANTAGONISTS
  申请人：E.I. DU PONT DE NEMOURS AND COMPANY

  公开号：EP0654027A1

  公开（公告）日：1995-05-24
• IMIDAZOLE 5-POSITION SUBSTITUTED ANGIOTENSIN II ANTAGONISTS
  申请人：THE DU PONT MERCK PHARMACEUTICAL COMPANY

  公开号：EP0711162A1

  公开（公告）日：1996-05-15
• EP0711162A4
  申请人：——

  公开号：EP0711162A4

  公开（公告）日：1996-09-04
• US5310929A
  申请人：——

  公开号：US5310929A

  公开（公告）日：1994-05-10