5-n-butyl-2,4-dihydro-4-<<2'-(N-trityltetrazol-5-yl)biphenyl-4-yl>methyl>-3H-1,2,4-triazol-3-one | 149810-21-9

• 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: 5-n-butyl-2,4-dihydro-4-<<2'-(N-trityltetrazol-5-yl)biphenyl-4-yl>methyl>-3H-1,2,4-triazol-3-one
• 英文别名: 5-butyl-2,4-dihydro-4-<<2-<1-(triphenylmethyl)-1H-tetrazol-5-yl><1,1'-biphenyl>-4'-yl>methyl>-3H-1,2,4-triazol-3-one；3-butyl-4-[[4-[2-(2-trityltetrazol-5-yl)phenyl]phenyl]methyl]-1H-1,2,4-triazol-5-one
• CAS: 149810-21-9
• 化学式: C₃₉H₃₅N₇O
• 分子量: 617.753
• InChiKey: MRJONPHSFJCPRJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.12
• 重原子数：
  47.0
• 可旋转键数：
  11.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  94.28
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  5-n-butyl-2,4-dihydro-4-<<2'-(N-trityltetrazol-5-yl)biphenyl-4-yl>methyl>-3H-1,2,4-triazol-3-one 在 sodium hydride 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 5.0h， 生成 5-butyl-2,4-dihydro-2-(2-naphthalenylmethyl)-4-<<2'-(1H-tetrazol-5-yl)<1,1'-biphenyl>-4-yl>methyl>-3H-1,2,4-triazol-3-one
  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
• 作为产物：
  描述：

  在 吡啶 、 trimethyltin azide 、 sodium methylate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 170.0h， 生成 5-n-butyl-2,4-dihydro-4-<<2'-(N-trityltetrazol-5-yl)biphenyl-4-yl>methyl>-3H-1,2,4-triazol-3-one
  参考文献：
  名称：

  Synthesis and structure-activity relationships of nonpeptide, potent triazolone-based angiotensin II receptor antagonists

  摘要：

  2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4'-yl]methyl] -3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2-phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized.

  DOI：

  10.1021/jm00067a015