2-chloro-4-(methylamino)pyrimidine-5-carbonitrile | 389606-74-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-chloro-4-(methylamino)pyrimidine-5-carbonitrile
• CAS: 389606-74-0
• 化学式: C₆H₅ClN₄
• 分子量: 168.585
• InChiKey: IKGUDRLCVAZUPF-UHFFFAOYSA-N

物化性质

• 沸点：
  416.5±30.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-amino-3-methoxyphenyl)(morpholino)methanone 、 2-chloro-4-(methylamino)pyrimidine-5-carbonitrile 在 三氟乙酸 作用下， 以 甲乙醚 为溶剂， 反应 18.0h， 生成 2-[2-methoxy-4-(morpholine-4-carbonyl)-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Discovery of Selective LRRK2 Inhibitors Guided by Computational Analysis and Molecular Modeling

  摘要：

  Mutations in the genetic sequence of leucine-rich repeat kinase 2 (LRRK2) have been linked to increased LRRK2 activity and risk for the development of Parkinson's disease (PD). Potent, and selective small molecules capable of inhibiting the kinase activity of LARK2 will be important tools for establishing a link between the kinase activity of LRRK2 and PD. In the absence of LRRK2 kinase domain crystal structures, a LRRK2 homology model was developed that provided robust guidance in the hit-to-lead optimization of small molecule LRRK2 inhibitors. Through a combination of molecular modeling, sequence analysis, and matched molecular pair (MMP) activity cliff analysis, a potent and selective lead inhibitor was discovered. The selectivity of this compound could be understood using the LRRK2 homology model, and application of this learning to a series of 2,4-diaminopyrimidine inhibitors in a scaffold hopping exercise led to the identification of highly potent and selective LRRK2 inhibitors that were also brain penetrable.

  DOI：

  10.1021/jm300452p
• 作为产物：
  描述：

  2,4-二氯-5-氰基嘧啶 、 甲胺 以 甲醇 、 乙醇 为溶剂， 生成 2-chloro-4-(methylamino)pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Discovery of Selective LRRK2 Inhibitors Guided by Computational Analysis and Molecular Modeling

  摘要：

  Mutations in the genetic sequence of leucine-rich repeat kinase 2 (LRRK2) have been linked to increased LRRK2 activity and risk for the development of Parkinson's disease (PD). Potent, and selective small molecules capable of inhibiting the kinase activity of LARK2 will be important tools for establishing a link between the kinase activity of LRRK2 and PD. In the absence of LRRK2 kinase domain crystal structures, a LRRK2 homology model was developed that provided robust guidance in the hit-to-lead optimization of small molecule LRRK2 inhibitors. Through a combination of molecular modeling, sequence analysis, and matched molecular pair (MMP) activity cliff analysis, a potent and selective lead inhibitor was discovered. The selectivity of this compound could be understood using the LRRK2 homology model, and application of this learning to a series of 2,4-diaminopyrimidine inhibitors in a scaffold hopping exercise led to the identification of highly potent and selective LRRK2 inhibitors that were also brain penetrable.

  DOI：

  10.1021/jm300452p

文献信息

• Trisubstituted pyrimidines
  申请人：Boehringer Ingelheim Pharma KG

  公开号：US20030134838A1

  公开（公告）日：2003-07-17

  The present invention relates to trisubstituted pyrimidines of formula 1 wherein R a to R e are defined as in claim 1, which are suitable for the treatment of illnesses in which &bgr;-amyloid modulators have a therapeutic benefit, the use thereof for preparing a pharmaceutical composition with the abovementioned properties, and processes for the preparation thereof.

  本发明涉及式1的三取代嘧啶，其中R至Re的定义如权利要求1中所述，适用于治疗β-淀粉样蛋白调节剂具有治疗效益的疾病，用于制备具有上述特性的药物组合物的用途，以及其制备方法。
• PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS
  申请人：Genentech, Inc.

  公开号：US20150051238A1

  公开（公告）日：2015-02-19

  Pyrazole compounds that are modulators of LRRK2, methods of making the compounds, and methods for using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

  Pyrazole化合物是LRRK2的调节剂，制备该化合物的方法以及使用该化合物治疗与LRRK2受体相关的疾病（如帕金森病）的方法。
• BICYCLIC PYRAZOLE LRRK2 SMALL MOLECULE INHIBITORS
  申请人：Genentech, Inc.

  公开号：US20150051201A1

  公开（公告）日：2015-02-19

  Compounds of formula I: or pharmaceutically acceptable salts thereof, wherein X, R 1 , R 2 , R 3 and A are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

  公式I的化合物：或其药学上可接受的盐，其中X，R1，R2，R3和A的定义如本文所述。还公开了制备这些化合物的方法，并使用这些化合物治疗与LRRK2受体相关的疾病，例如帕金森病。
• PYRIMIDINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1303496B1

  公开（公告）日：2007-09-12
• 5-SUBSTITUIERTE 4-AMINO-2-PHENYLAMINO-PYRIMDINDERIVATE UND IHRE VERWENDUNG ALS BETA-AMYLOID MODULATOREN
  申请人：Boehringer Ingelheim Pharma GmbH & Co.KG

  公开号：EP1453516A2

  公开（公告）日：2004-09-08