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 | 139964-19-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 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
• 英文名称: 4-ethyl-2-n-propyl-1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)-methyl)imidazole-5-carboxylic acid
• 英文别名: 4-ethyl-2-propyl-1-[[2'-(tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylic acid；4-ethyl-2-n-propyl-1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl) methyl)imidazole-5-carboxylic acid；4-Ethyl-2-propyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid；4-ethyl-2-propyl-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-5-carboxylic acid；4-Ethyl-2-propyl-1-(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methylimidazole-5-carboxylic acid；5-ethyl-2-propyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid
• CAS: 139964-19-5
• 化学式: C₂₃H₂₄N₆O₂
• 分子量: 416.483
• InChiKey: OFYWYKMCRWMPPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 4.0h， 生成 (1,3-dioxa-5-methyl-cyclopentene-2-one-4-yl)methyl 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
• 作为产物：
  描述：

  methyl 4-ethyl-2-propyl-1-[(2'-(1H-tetrazol-5-yl)-biphenyl-5-yl)methyl]imidazole-5-carboxylic acid 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 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
  参考文献：
  名称：

  4-Alkylimidazole derivatives and anti-hypertensive use thereof

  摘要：

  血管紧张素II拮抗剂降压化合物，例如##STR1##其中R.sup.2为--CHO或--COOH，R.sup.1为乙基，具有出色的口服效能。

  公开号：

  US05137902A1

文献信息

• Prodrugs of imidazole carboxylic acids as angiotensin II receptor
  申请人：E. I. Du Pont de Nemours and Company

  公开号：US05310929A1

  公开（公告）日：1994-05-10

  Prodrugs of imidazole carboxylic acids which are AII antagonists useful in treating hypertension, pharmaceutical compositions thereof and a method of treating hypertension using such prodrugs are disclosed.

  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。
• Nonpeptide Angiotensin II Receptor Antagonists:  Synthesis, Biological Activities, and Structure−Activity Relationships of Imidazole-5-carboxylic Acids Bearing Alkyl, Alkenyl, and Hydroxyalkyl Substituents at the 4-Position and Their Related Compounds
  作者：Hiroaki Yanagisawa、Yoshiya Amemiya、Takuro Kanazaki、Yasuo Shimoji、Koichi Fujimoto、Yoshiko Kitahara、Toshio Sada、Makoto Mizuno、Masahiro Ikeda、Shuichi Miyamoto、Youji Furukawa、Hiroyuki Koike

  DOI：10.1021/jm950450f

  日期：1996.1.1

  A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)-imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response

  制备了一系列在4-位带有烷基，烯基和羟烷基取代基的咪唑-5-羧酸及其相关化合物，并评估了它们对血管紧张素II（AII）受体的拮抗活性。其中，4-（1-羟烷基）-咪唑衍生物对AII受体具有很强的结合亲和力，并通过静脉内给药有效地抑制了AII诱导的升压反应。这些酸的各种酯通过口服显示出有效和持久的拮抗活性。最有前途的化合物是（5-甲基-2-氧代-1,3-二氧杂-4-基）甲基（CS-866）和4-（1-羟基-1-甲基乙基）-的（新戊酰氧基）-甲基酯2-丙基-1-[（（2'-1H-四唑-5-基联苯-4-基）-甲基]咪唑-5-羧酸（26c）。
• Use of angiotensin II subtype 1 (AT1) antagonists for the manufacture of a medicament in the treatment of premenstrual syndrome
  申请人：DePadova, Anthony S.

  公开号：EP1393722A2

  公开（公告）日：2004-03-03

  The present invention relates to a method of modifying Angiotensin II subtype 1 (AT1) receptor activity for the treatment of premenstrual syndrome (PMS) and the symptoms associated therewith, and further relates to a method for the treatment of acute or chronic pain mediated by the sympathetic nervous system. The treatment includes the administration of an effective amount of an AT1 antagonist. AT1 antagonists are drugs that are capable of blocking AT1 receptors present within the body throughout the central nervous system including the hypothalamus. By blocking the AT1 receptor activity, hypothalamic nerve activity, and therefore, sympathetic nerve activity are modulated. Thus, an effective method for treating sympathetically mediated pain is provided, as well as an effective method for treating PMS. The AT1 antagonist can be used alone or in combination with other drug therapies, for instance, non-steroidal anti-inflammatory drugs, antidepressants, opiod drugs, angiotensin converting enzyme inhibitors, and diuretics.

  本发明涉及一种改变血管紧张素II亚型1（AT1）受体活性以治疗经前期综合征（PMS）及其相关症状的方法，还涉及一种治疗由交感神经系统介导的急性或慢性疼痛的方法。治疗方法包括施用有效量的AT1拮抗剂。AT1拮抗剂是一种能够阻断体内存在于包括下丘脑在内的整个中枢神经系统中的AT1受体的药物。通过阻断 AT1 受体的活性，可调节下丘脑神经活动，从而调节交感神经活动。因此，我们提供了一种治疗交感神经介导的疼痛的有效方法，以及一种治疗经前综合症的有效方法。AT1拮抗剂可以单独使用，也可以与其他药物疗法结合使用，例如非甾体抗炎药、抗抑郁药、阿片类药物、血管紧张素转换酶抑制剂和利尿剂。
• 4-ALKYLIMIDAZOLE DERIVATIVES
  申请人：E.I. DU PONT DE NEMOURS AND COMPANY

  公开号：EP0539509B1

  公开（公告）日：1995-04-12
• 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