(3aR,6aR)-4'-(octahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile | 948846-59-1

• 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: (3aR,6aR)-4'-(octahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile
• 英文别名: (3aR,6aR)-4'-(hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile；4-[4-[(3aR,6aR)-3,3a,4,5,6,6a-hexahydro-2H-pyrrolo[2,3-c]pyrrol-1-yl]phenyl]benzonitrile
• CAS: 948846-59-1
• 化学式: C₁₉H₁₉N₃
• 分子量: 289.38
• InChiKey: IGMGYMIIMYWOOO-MJGOQNOKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  39.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3aR,6aR)-4'-(octahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile 、 1-碘代丙烷 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以55.5%的产率得到4'-[(3aR,6aR)-5-propyloctahydropyrrolo[3,4-b]pyrrol-1(2H)-yl]-1,1'-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
• 作为产物：
  描述：

  N1-Boc-(3aR,6aR)-六氢吡咯[3,4-b]吡咯 在 palladium diacetate 、 2,2'-双(二苯基磷)联苯 三氟乙酸 、 sodium t-butanolate 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 20.5h， 生成 (3aR,6aR)-4'-(octahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile
  参考文献：
  名称：

  WO2007/100990

  摘要：

  公开号：

文献信息

• Octahydro-pyrrolo[3,4-b]pyrrole Derivatives
  申请人：Cowart D. Marlon

  公开号：US20070232612A1

  公开（公告）日：2007-10-04

  Octahydro-pyrrolo[3,4-b]pyrrole derivatives are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands, Octahydro-pyrrolo[3,4-b]pyrrole compounds, methods for using such compounds, compositions for making them, and processes for preparing such compounds are disclosed herein.

  本文披露了八氢吡咯并[3,4-b]吡咯衍生物在治疗由组胺-3受体配体预防或改善的疾病或疾患方面的用途，包括八氢吡咯并[3,4-b]吡咯化合物，使用这种化合物的方法，制备它们的组合物以及制备这种化合物的过程。
• Octahydro-pyrrolo[3,4-b]pyrrole derivatives
  申请人：Abbott Laboratories

  公开号：US07728031B2

  公开（公告）日：2010-06-01

  Octahydro-pyrrolo[3,4-b]pyrrole derivatives are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands, Octahydro-pyrrolo[3,4-b]pyrrole compounds, methods for using such compounds, compositions for making them, and processes for preparing such compounds are disclosed herein.

  本文揭示了八氢吡咯[3,4-b]吡咯衍生物在治疗由组胺-3受体配体预防或改善的疾病或疾患中的用途，八氢吡咯[3,4-b]吡咯化合物，使用这些化合物的方法，制备它们的组合物以及制备这些化合物的过程。
• OCTAHYDRO-PYRROLO[3,4-B]PYRROLE DERIVATIVES
  申请人：Cowart Marlon D.

  公开号：US20100222358A1

  公开（公告）日：2010-09-02

  Octahydro-pyrrolo[3,4-b]pyrrole derivatives are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands. Octahydro-pyrrolo[3,4-b]pyrrole compounds, methods for using such compounds, compositions for making them, and processes for preparing such compounds are disclosed herein.

  八氢吡咯并[3,4-b]吡咯衍生物在治疗因组胺-3受体配体预防或改善的疾病或疾患中具有用途。本文揭示了八氢吡咯并[3,4-b]吡咯化合物，使用这种化合物的方法，制备它们的组合物以及制备这种化合物的过程。
• Octahydro-pyrrolo[3,4-B]pyrrole derivatives
  申请人：Cowart Marlon D.

  公开号：US08399468B2

  公开（公告）日：2013-03-19

  Octahydro-pyrrolo[3,4-b]pyrrole derivatives are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands. Octahydro-pyrrolo[3,4-b]pyrrole compounds, methods for using such compounds, compositions for making them, and processes for preparing such compounds are disclosed herein.

  八氢吡咯并[3,4-b]吡咯衍生物在治疗由组胺-3受体配体预防或改善的病症或障碍方面是有用的。本文揭示了八氢吡咯并[3,4-b]吡咯化合物，使用这些化合物的方法，制备它们的组成部分以及制备这些化合物的过程。
• US7728031B2
  申请人：——

  公开号：US7728031B2

  公开（公告）日：2010-06-01