(3aS,6aS)-4'-(5-methyl-octahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile | 1176846-85-7

• 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: (3aS,6aS)-4'-(5-methyl-octahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile
• 英文别名: 4-[4-[(3aS,6aS)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[2,3-c]pyrrol-1-yl]phenyl]benzonitrile
• CAS: 1176846-85-7
• 化学式: C₂₀H₂₁N₃
• 分子量: 303.407
• InChiKey: CXRCFQKCULIFAC-AZUAARDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  30.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (3aS,6aS)-1-(4-bromo-phenyl)-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole 、 4-氰基苯硼酸 在 potassium phosphate 、 palladium diacetate 、 2-(二环己基膦基)联苯 作用下， 以 水 、 异丙醇 、 甲苯 为溶剂， 以3.1 mg的产率得到(3aS,6aS)-4'-(5-methyl-octahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile
  参考文献：
  名称：

  Design of a New Histamine H₃ Receptor Antagonist Chemotype: (3aR,6aR)-5-Alkyl-1-aryl-octahydropyrrolo[3,4-b]pyrroles, Synthesis, and Structure−Activity Relationships

  摘要：

  A new histamine H-3 receptor (H3R) antagonist chemotype 1 was designed by combining key pharmacophoric elements from two different precursor structural series and then simplifying and optimizing the resulting combined structural features. First, analogues were made based oil a previously identified conessine-based H3R. antagonist series. While the first analogues 11 and 15 showed no antagonistic activity to H3R, the mere addition of a key moiety found in the reference compound 7 (ABT-239) elevated the series to high potency at H3R. The hybrid structure (16b) was judged too synthetically demanding to enable an extensive SAR study, thus forcing a strategy to simplify the chemical structure. The resulting (3aR,6aR)-5-alkyl-1-aryl-octahydropyrrolo[3,4-b]pyrrole series proved to be highly potent, as exemplified by 17a having a human H-3 K-i of 0.54 nM, rat H-3 K-i of 4.57 nM, and excellent pharmacokinetics (PK) profile in rats (oral bioavailability of 39% and t(1/2) of 2.4 h).

  DOI：

  10.1021/jm900480x