2-butyl-3-{[3-fluoro-(2'-tert-butylaminosulfonyl)-4-biphenylyl]methyl}-4,5-dihydro-3H-imidazo[4,5-c]pyridin-4-one | 177264-20-9

• 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-butyl-3-{[3-fluoro-(2'-tert-butylaminosulfonyl)-4-biphenylyl]methyl}-4,5-dihydro-3H-imidazo[4,5-c]pyridin-4-one
• 英文别名: N-tert-butyl-2-[4-[(2-butyl-4-oxo-5H-imidazo[4,5-c]pyridin-3-yl)methyl]-3-fluorophenyl]benzenesulfonamide
• CAS: 177264-20-9
• 化学式: C₂₇H₃₁FN₄O₃S
• 分子量: 510.633
• InChiKey: JBWTUBUJSUCTEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-butyl-3-{[3-fluoro-(2'-tert-butylaminosulfonyl)-4-biphenylyl]methyl}-4,5-dihydro-3H-imidazo[4,5-c]pyridin-4-one 在 potassium tert-butylate 、 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
• 作为产物：
  描述：

  2-butyl-4,5-dihydro-4-oxo-3H-imidazo<4,5-c>pyridine 、 [3-Fluoro-2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl Bromide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以5.4%的产率得到N-tert-butyl-2-[4-[[2-butyl-3-[[4-[2-(tert-butylsulfamoyl)phenyl]-2-fluorophenyl]methyl]-4-oxoimidazo[4,5-c]pyridin-5-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

文献信息

• 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
  作者：W.W.K.R. Mederski、D Dorsch、M Osswald、H Schwartz、N Beier、M Christadler、K.O. Minck、P Schelling、C.J. Schmitges

  DOI：10.1016/s0223-5234(97)84011-1

  日期：1997.6

  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.