1-butyl-6-chloro-2,3-dihydro-2-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl]-1,1'-biphenyl-4-yl]methyl]-1H-pyrazolo[3,4-b]pyridin-3-one | 1016230-45-7

• 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: 1-butyl-6-chloro-2,3-dihydro-2-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl]-1,1'-biphenyl-4-yl]methyl]-1H-pyrazolo[3,4-b]pyridin-3-one
• 英文别名: 1-Butyl-6-chloro-2-[[4-[2-(2-trityltetrazol-5-yl)phenyl]phenyl]methyl]pyrazolo[3,4-b]pyridin-3-one
• CAS: 1016230-45-7
• 化学式: C₄₃H₃₆ClN₇O
• 分子量: 702.258
• InChiKey: YJRHPIGNQRPJPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.7
• 重原子数：
  52
• 可旋转键数：
  11
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  80
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-butyl-6-chloro-2,3-dihydro-2-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl]-1,1'-biphenyl-4-yl]methyl]-1H-pyrazolo[3,4-b]pyridin-3-one 在 甲酸 作用下， 以 二氯甲烷 为溶剂， 以49%的产率得到1-butyl-6-chloro-2-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]pyrazolo[3,4-b]pyridin-3-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of AT₁ Angiotensin II Receptor Antagonists Based on the Pyrazolo[3,4-b]pyridine and Related Heteroaromatic Bicyclic Systems

  摘要：

  Novel AT(1) receptor antagonists bearing the pyrazolo[3,4-b]pyridine bicyclic heteroaromatic system (or structurally related moieties) were designed and synthesized as the final step of a large program devoted to the development of new anti hypertensive agents and to the understanding of the molecular basis of their pharmacodynamic and pharmacokinetic properties. The preliminary pharmacological characterization revealed nanomolar AT(1) receptor affinity for several compounds of the series and a potent antagonistic activity in isolated rabbit aortic strip functional assay for 7c and 8a. These results stimulated the study of the biopharmaceutical properties of some selected compounds, which were found to be characterized by a permeability from medium to high. Remarkably, the least permeable 7c showed both permeability and oral bioavailability (80%) higher than losartan, but its terminal half-life was shorter. These results suggest that the permeability is not a limiting factor in the pharmacokinetics of these AT(1) receptor antagonists.

  DOI：

  10.1021/jm7011563
• 作为产物：
  描述：

  2-(4-bromobenzyl)-1-butyl-6-chloro-2,3-dihydro-1H-pyrazolo[3,4-b]pyridin-3-one 、 2 -(5-(1-三苯甲基-1H-四氮唑)苯硼酸 在 palladium diacetate potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 以11%的产率得到1-butyl-6-chloro-2,3-dihydro-2-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl]-1,1'-biphenyl-4-yl]methyl]-1H-pyrazolo[3,4-b]pyridin-3-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of AT₁ Angiotensin II Receptor Antagonists Based on the Pyrazolo[3,4-b]pyridine and Related Heteroaromatic Bicyclic Systems

  摘要：

  Novel AT(1) receptor antagonists bearing the pyrazolo[3,4-b]pyridine bicyclic heteroaromatic system (or structurally related moieties) were designed and synthesized as the final step of a large program devoted to the development of new anti hypertensive agents and to the understanding of the molecular basis of their pharmacodynamic and pharmacokinetic properties. The preliminary pharmacological characterization revealed nanomolar AT(1) receptor affinity for several compounds of the series and a potent antagonistic activity in isolated rabbit aortic strip functional assay for 7c and 8a. These results stimulated the study of the biopharmaceutical properties of some selected compounds, which were found to be characterized by a permeability from medium to high. Remarkably, the least permeable 7c showed both permeability and oral bioavailability (80%) higher than losartan, but its terminal half-life was shorter. These results suggest that the permeability is not a limiting factor in the pharmacokinetics of these AT(1) receptor antagonists.

  DOI：

  10.1021/jm7011563