{3-Butyl-5-oxo-4-[2'-(2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5-dihydro-[1,2,4]triazol-1-yl}-phenyl-acetic acid methyl ester | 133690-24-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: {3-Butyl-5-oxo-4-[2'-(2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5-dihydro-[1,2,4]triazol-1-yl}-phenyl-acetic acid methyl ester
• 英文别名: 5-n-Butyl-2-[alpha-(carbomethoxy)benzyl]-2,4-dihydro-4-[[2'-(5-tetrazolyl)biphenyl-4-yl]methyl]-3H-1,2,4-triazol-3-one；methyl 2-[3-butyl-5-oxo-4-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-1,2,4-triazol-1-yl]-2-phenylacetate
• CAS: 133690-24-1
• 化学式: C₂₉H₂₉N₇O₃
• 分子量: 523.594
• InChiKey: WPQQQVTXYDQTAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  {3-Butyl-5-oxo-4-[2'-(2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5-dihydro-[1,2,4]triazol-1-yl}-phenyl-acetic acid methyl ester 在 silica gel 作用下， 以 四氢呋喃 为溶剂， 以to give the title compound in 50% yield的产率得到{3-Butyl-5-oxo-4-[2'-(2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5-dihydro-[1,2,4]triazol-1-yl}-phenyl-acetic acid
  参考文献：
  名称：

  Substituted triazolinones, triazolinethiones, and triazolinimines as

  摘要：

  公开了一种新的取代三唑酮，三唑硫酮和三唑亚胺化合物，可用作血管紧张素II拮抗剂。这些化合物具有以下一般公式：## STR1 ##其中G是R.sup.1或## STR2 ##。

  公开号：

  US05411980A1
• 作为产物：
  描述：

  5-[4’-(溴甲基)-[1,1’-联苯]-2-基]-2-(三苯基甲基)-2H-四氮唑 在 叠氮化锂 、 水 、 sodium hydride 、 溶剂黄146 、 三苯基膦 作用下， 以 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 37.5h， 生成 {3-Butyl-5-oxo-4-[2'-(2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5-dihydro-[1,2,4]triazol-1-yl}-phenyl-acetic acid methyl ester
  参考文献：
  名称：

  Triazolinones as nonpeptide angiotensin II antagonists. 1. Synthesis and evaluation of potent 2,4,5-trisubstituted triazolinones

  摘要：

  A series of 2,4-dihydro-2,4,5-trisubstituted-3H-1,2,4-triazol-3-ones was prepared via several synthetic routes and evaluated as AII receptor antagonists in vitro and in vivo. The preferred compounds contained a [2'-(5-tetrazolyl)biphenyl-4-yl]methyl side chain at N4 and an n-butyl group at C5. A number of these bearing an alkyl or aralkyl substituent at N2 showed in vitro potency in the nanomolar range (rabbit aorta membrane receptor), and several of these, e.g., the 2,2-dimethyl-1-propyl analogue (54, IC50 = 2.1 nM), effectively blocked the AII pressor response in conscious rats with significant duration (2.5 h at 1 mg/kg orally for 54). Among analogues possessing aryl substituents at N2, ortho substitution on the phenyl moiety resulted in several derivatives with in vitro potency in the low nanomolar range. One of these, featuring a 2-(trifluoromethyl)phenyl substituent at N2 (25, IC50 = 1.2 nM), was effective at 1 mg/kg orally in the rat model, with a duration of >6 h. Implications for hydrophobic and hydrogen-bonding interactions with the AT1 receptor are discussed.

  DOI：

  10.1021/jm00069a015

文献信息

• Substituted triazolinones, triazolinethiones, and triazolinimines as
  申请人：Merck & Co., Inc.

  公开号：US05411980A1

  公开（公告）日：1995-05-02

  There are disclosed new substituted triazolinone, triazolinethione, and triazolinimine compounds which are useful as angiotensin II antagonists. These compounds have the general formula: ##STR1## wherein G is R.sup.1 or ##STR2##

  已披露了新的取代三唑酮，三唑硫酮和三唑亚胺化合物，这些化合物可用作血管紧张素II拮抗剂。这些化合物具有一般式：##STR1## 其中G为R.sup.1或##STR2##
• Substituted triazolinones, triazolinethiones, and triazolinimines as angiotensin II antagonists
  申请人：MERCK & CO. INC.

  公开号：EP0412594A2

  公开（公告）日：1991-02-13

  There are disclosed new substituted triazolinone, triazolinethione, and triazolinimine compounds which are useful as angiotensin II antagonists. These compounds have the general formula:

  公开了可用作血管紧张素 II 拮抗剂的新的取代三唑啉酮、三唑啉硫酮和三唑啉亚胺化合物。这些化合物的通式如下
• US5411980A
  申请人：——

  公开号：US5411980A

  公开（公告）日：1995-05-02
• Triazolinones as nonpeptide angiotensin II antagonists. 1. Synthesis and evaluation of potent 2,4,5-trisubstituted triazolinones
  作者：Linda L. Chang、Wallace T. Ashton、Kelly L. Flanagan、Robert A. Strelitz、Malcolm MacCoss、William J. Greenlee、Raymond S. L. Chang、Victor J. Lotti、Kristie A. Faust

  DOI：10.1021/jm00069a015

  日期：1993.8

  A series of 2,4-dihydro-2,4,5-trisubstituted-3H-1,2,4-triazol-3-ones was prepared via several synthetic routes and evaluated as AII receptor antagonists in vitro and in vivo. The preferred compounds contained a [2'-(5-tetrazolyl)biphenyl-4-yl]methyl side chain at N4 and an n-butyl group at C5. A number of these bearing an alkyl or aralkyl substituent at N2 showed in vitro potency in the nanomolar range (rabbit aorta membrane receptor), and several of these, e.g., the 2,2-dimethyl-1-propyl analogue (54, IC50 = 2.1 nM), effectively blocked the AII pressor response in conscious rats with significant duration (2.5 h at 1 mg/kg orally for 54). Among analogues possessing aryl substituents at N2, ortho substitution on the phenyl moiety resulted in several derivatives with in vitro potency in the low nanomolar range. One of these, featuring a 2-(trifluoromethyl)phenyl substituent at N2 (25, IC50 = 1.2 nM), was effective at 1 mg/kg orally in the rat model, with a duration of >6 h. Implications for hydrophobic and hydrogen-bonding interactions with the AT1 receptor are discussed.