propyl 4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5-carboxylate | 154749-90-3

• 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: propyl 4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5-carboxylate
• 英文别名: propyl 5-ethyl-2-propyl-3-[[4-[2-(1-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate
• CAS: 154749-90-3
• 化学式: C₄₅H₄₄N₆O₂
• 分子量: 700.883
• InChiKey: TWIUXWIBCDIOOW-UHFFFAOYSA-N

物化性质

• 沸点：
  862.0±75.0 °C(predicted)
• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.4
• 重原子数：
  53
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  87.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  propyl 4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5-carboxylate 在 盐酸 silica gel 、 silica 、 二氯甲烷 、 甲醇 、 氯仿 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以to provide 0.25 g of the title compound的产率得到propyl 4-ethyl-2-propyl-1-[[2'-(tetrazol-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：

  本发明涉及咪唑羧酸的前药，其为AII受体拮抗剂，可用于治疗高血压，还涉及这些前药的制药组合物以及使用这些前药治疗高血压的方法。

  公开号：

  US05310929A1
• 作为产物：
  描述：

  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 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 propyl 4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(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

文献信息

• US5310929A
  申请人：——

  公开号：US5310929A

  公开（公告）日：1994-05-10
• [EN] PRODRUGS OF IMIDAZOLE CARBOXYLIC ACIDS AS ANGIOTENSIN II RECEPTOR ANTAGONISTS<br/>[FR] PROMEDICAMENTS D'ACIDES CARBOXYLIQUES D'IMIDAZOLE EN TANT QU'ANTAGONISTES DES RECEPTEURS DE L'ANGIOTENSINE II
  申请人：E.I. DU PONT DE NEMOURS AND COMPANY

  公开号：WO1994003435A1

  公开（公告）日：1994-02-17

  (EN) Prodrugs of imidazole carboxylic acids of formula I which are AII antagonists useful in treating hypertension, pharmaceutical compositions thereof and a method of treating hypertension using such prodrugs are disclosed.(FR) L'invention concerne des promédicaments d'acides carboxyliques d'imidazole représentés par la formule (I), qui sont des antagonistes de l'angiotensine II utiles dans le traitement de l'hypertension. L'invention se rapporte également à des compositions pharmaceutiques contenant ces promédicaments et à un procédé de traitement de l'hypertension au moyen de ces derniers.