[5-(6-chlorobenzothiazol-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(2,6-dimethoxyphenyl)methanone

• 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: [5-(6-chlorobenzothiazol-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(2,6-dimethoxyphenyl)methanone
• 英文别名: [(3aS,6aR)-2-(6-chloro-1,3-benzothiazol-2-yl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(2,6-dimethoxyphenyl)methanone
• 化学式: C₂₂H₂₂ClN₃O₃S
• 分子量: 443.954
• InChiKey: KQRJYENNYTUWHU-OKILXGFUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  83.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  cis-3-benzyl-3,7-diazabicyclo[3.3.0]octane 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、482.64 kPa 条件下， 反应 117.0h， 生成 [5-(6-chlorobenzothiazol-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(2,6-dimethoxyphenyl)methanone
  参考文献：
  名称：

  Novel Octahydropyrrolo[3,4-c]pyrroles Are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate

  摘要：

  The preclinical characterization of novel octahydropyrrolo[3,4-c]pyrroles that are potent land selective orexin-2 antagonists is described-Optimization of physicochemical and DMPK properties led to the discovery of Compounds with tissue distribution and duration of action suitable for evaluation in the treatment of primary insomnia. These selective orexin-2 antagonists are proven to promote sleep in rats, and this work ultimately led to the identification of a compound that progressed into human clinical trials for the treatment Of primary insomnia. The synthesis, SAR, and optimization, of the pharmacokinetic properties of this series of compounds as well as the identification of the clinical candidate, JNJ-42847922 (34), are described herein.

  DOI：

  10.1021/acs.jmedchem.5b00742

文献信息

• Novel Octahydropyrrolo[3,4-<i>c</i>]pyrroles Are Selective Orexin-2 Antagonists: SAR Leading to a Clinical Candidate
  作者：Michael A. Letavic、Pascal Bonaventure、Nicholas I. Carruthers、Christine Dugovic、Tatiana Koudriakova、Brian Lord、Timothy W. Lovenberg、Kiev S. Ly、Neelakandha S. Mani、Diane Nepomuceno、Daniel J. Pippel、Michele Rizzolio、Jonathan E. Shelton、Chandra R. Shah、Brock T. Shireman、Lana K. Young、Sujin Yun

  DOI：10.1021/acs.jmedchem.5b00742

  日期：2015.7.23

  The preclinical characterization of novel octahydropyrrolo[3,4-c]pyrroles that are potent land selective orexin-2 antagonists is described-Optimization of physicochemical and DMPK properties led to the discovery of Compounds with tissue distribution and duration of action suitable for evaluation in the treatment of primary insomnia. These selective orexin-2 antagonists are proven to promote sleep in rats, and this work ultimately led to the identification of a compound that progressed into human clinical trials for the treatment Of primary insomnia. The synthesis, SAR, and optimization, of the pharmacokinetic properties of this series of compounds as well as the identification of the clinical candidate, JNJ-42847922 (34), are described herein.