2-[4-[[2-Butyl-4-oxo-5-(2-oxo-2-piperidin-1-ylethyl)imidazo[4,5-c]pyridin-3-yl]methyl]-3-fluorophenyl]benzenesulfonamide | 1027145-73-8

• 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: 2-[4-[[2-Butyl-4-oxo-5-(2-oxo-2-piperidin-1-ylethyl)imidazo[4,5-c]pyridin-3-yl]methyl]-3-fluorophenyl]benzenesulfonamide
• CAS: 1027145-73-8
• 化学式: C₃₀H₃₄FN₅O₄S
• 分子量: 579.695
• InChiKey: JOUBFLXJIVZVTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-苯丙酰氯 、 2-[4-[[2-Butyl-4-oxo-5-(2-oxo-2-piperidin-1-ylethyl)imidazo[4,5-c]pyridin-3-yl]methyl]-3-fluorophenyl]benzenesulfonamide 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 反应 48.0h， 以84%的产率得到2-butyl-3-{[3-fluoro-2'-(3-phenylethylcarboxamidosulfonyl)-4-biphenylyl]methyl}-4,5-dihydro-5-[(2-oxo-2-piperidino)ethyl]-3H-imidazo[4,5-c]pyridin-4-one
  参考文献：
  名称：

  Novel 4,5-dihydro-4-oxo-3H-imidazo[4,5-c]pyridines. Potent angiotensin II receptor antagonists with high affinity for both the AT1 and AT2 subtypes

  摘要：

  The synthesis and pharmacological activity of balanced high affinity non-peptide angiotensin II antagonists of the AT(1) and AT(2) subtype receptors have been presented. A series of previously prepared AT(1) selective 4,5-dihydro-4-oxo-3H-imidazo[4,5-c]pyridines were modified at four different positions in order to increase the AT(2) binding affinity by maintaining the nanomolar activity for the AT(1) receptor. The targeted AT(2)/AT(1) IC50 binding ratio of similar to 1 was achieved with a number of compounds possessing a small alkyl chain at C-2, different acetamide groups at N-5 and a 3-fluoro and 2'-carboxamidosulfonyl substituent at the biphenylmethyl moiety. These modifications led to analogue 12s, which exhibited an AT(2)/AT(1) ratio of 0.74, a subnanomolar AT(1) antagonistic potency (0.18 nM) and a high metabolic stability in rat and monkey liver microsomes in vitro. After oral administration of 3 mg/kg to cynomolgus monkeys, EMD 90423 (potassium salt of 12s) demonstrated good efficacy and a long duration of action as an antihypertensive agent.

  DOI：

  10.1016/s0223-5234(97)84011-1
• 作为产物：
  描述：

  [3-Fluoro-2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl Bromide 在 potassium tert-butylate 、 potassium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 2-[4-[[2-Butyl-4-oxo-5-(2-oxo-2-piperidin-1-ylethyl)imidazo[4,5-c]pyridin-3-yl]methyl]-3-fluorophenyl]benzenesulfonamide
  参考文献：
  名称：

  Novel 4,5-dihydro-4-oxo-3H-imidazo[4,5-c]pyridines. Potent angiotensin II receptor antagonists with high affinity for both the AT1 and AT2 subtypes

  摘要：

  The synthesis and pharmacological activity of balanced high affinity non-peptide angiotensin II antagonists of the AT(1) and AT(2) subtype receptors have been presented. A series of previously prepared AT(1) selective 4,5-dihydro-4-oxo-3H-imidazo[4,5-c]pyridines were modified at four different positions in order to increase the AT(2) binding affinity by maintaining the nanomolar activity for the AT(1) receptor. The targeted AT(2)/AT(1) IC50 binding ratio of similar to 1 was achieved with a number of compounds possessing a small alkyl chain at C-2, different acetamide groups at N-5 and a 3-fluoro and 2'-carboxamidosulfonyl substituent at the biphenylmethyl moiety. These modifications led to analogue 12s, which exhibited an AT(2)/AT(1) ratio of 0.74, a subnanomolar AT(1) antagonistic potency (0.18 nM) and a high metabolic stability in rat and monkey liver microsomes in vitro. After oral administration of 3 mg/kg to cynomolgus monkeys, EMD 90423 (potassium salt of 12s) demonstrated good efficacy and a long duration of action as an antihypertensive agent.

  DOI：

  10.1016/s0223-5234(97)84011-1