8-[2'-(2-tert-Butyl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-5-hydroxy-2-hydroxymethyl-4-methyl-8H-pyrido[2,3-d]pyrimidin-7-one | 215437-38-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-[2'-(2-tert-Butyl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-5-hydroxy-2-hydroxymethyl-4-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
• 英文别名: 8-[[4-[2-(2-Tert-butyltetrazol-5-yl)phenyl]phenyl]methyl]-5-hydroxy-2-(hydroxymethyl)-4-methylpyrido[2,3-d]pyrimidin-7-one
• CAS: 215437-38-0
• 化学式: C₂₇H₂₇N₇O₃
• 分子量: 497.556
• InChiKey: LYLLHTIMGWLLEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-[2'-(2-tert-Butyl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-5-hydroxy-2-hydroxymethyl-4-methyl-8H-pyrido[2,3-d]pyrimidin-7-one 在 三氟甲磺酸 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以67%的产率得到5-Hydroxy-2-hydroxymethyl-4-methyl-8-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-8H-pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Metabolites of the Angiotensin II Antagonist Tasosartan:  The Importance of a Second Acidic Group

  摘要：

  Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensin II antagonist series, a second acidic group can improve receptor binding activity but decrease in vivo activity after oral dosing. The metabolic introduction of a second acidic group in tasosartan bypasses this problem and contributes to the excellent profile of the compound. A molecular modeling study provides a rationale for the role of the enol group of 8 in AT(1) receptor binding.

  DOI：

  10.1021/jm970690q
• 作为产物：
  描述：

  2-methoxymethyl-4-chloro-5-(1-ethoxyvinyl)-6-methylpyrimidine 在 盐酸 、 三溴化硼 、 sodium hydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二氯甲烷 、 正丁醇 为溶剂， 反应 55.0h， 生成 8-[2'-(2-tert-Butyl-2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-5-hydroxy-2-hydroxymethyl-4-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Metabolites of the Angiotensin II Antagonist Tasosartan:  The Importance of a Second Acidic Group

  摘要：

  Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensin II antagonist series, a second acidic group can improve receptor binding activity but decrease in vivo activity after oral dosing. The metabolic introduction of a second acidic group in tasosartan bypasses this problem and contributes to the excellent profile of the compound. A molecular modeling study provides a rationale for the role of the enol group of 8 in AT(1) receptor binding.

  DOI：

  10.1021/jm970690q