(R)-2-aminopropanenitrile hydrochloride | 1385022-43-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (R)-2-aminopropanenitrile hydrochloride
• 英文别名: (2R)-2-aminopropanenitrile hydrochloride；(2R)-2-aminopropanenitrile;hydrochloride
• CAS: 1385022-43-4
• 化学式: C₃H₆N₂*ClH
• mdl: MFCD22628484
• 分子量: 106.555
• InChiKey: WJGQCCPNVRCAQI-AENDTGMFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.52
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-2-aminopropanenitrile hydrochloride 、 (1R,2R)-2-(8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexane-1-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以46%的产率得到(1R,2R)-N-[(1R)-1-cyanoethyl]-2-(8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide
  参考文献：
  名称：

  (1R,2R)-N-(1-Cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): A Potent and Highly Selective Cathepsin K Inhibitor for the Treatment of Osteoarthritis

  摘要：

  Directed screening of nitrile compounds revealed 3 as a highly potent cathepsin K inhibitor but with cathepsin S activity and very poor stability to microsomes. Synthesis of compounds with reduced molecular complexity, such as 7, revealed key SAR and demonstrated that baseline physical properties and in vitro stability were in fact excellent for this series. The tricycle carboline P3 unit was discovered by hypothesis-based design using existing structural information. Optimization using small substituents, knowledge from matched molecular pairs, and control of lipophilicity yielded compounds very close to the desired profile, of which 34 (AZD4996) was selected on the basis of pharmacokinetic profile.

  DOI：

  10.1021/jm3007257