2-[2-methoxy-4-(morpholine-4-carbonyl)-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile | 1351761-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2-[2-methoxy-4-(morpholine-4-carbonyl)-phenylamino]-4-methylamino-pyrimidine-5-carbonitrile
• 英文别名: 2-[2-methoxy-4-(morpholine-4-carbonyl)anilino]-4-(methylamino)pyrimidine-5-carbonitrile
• CAS: 1351761-98-2
• 化学式: C₁₈H₂₀N₆O₃
• 分子量: 368.395
• InChiKey: LYEWAGXEEPXHOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4-二氯-5-氰基嘧啶 在 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 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

文献信息

• AMINOPYRIMIDINE DERIVATIVES AS LRRK2 INHIBITORS
  申请人：Baker-Glenn Charles

  公开号：US20110301141A1

  公开（公告）日：2011-12-08

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R 1 , R 2 , R 3 , R 5 , R 6 and R 7 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.

  化合物的公式I：或其药用盐，其中m，n，X，R1，R2，R3，R5，R6和R7的定义如本文所述。还公开了制备这些化合物的方法以及将这些化合物用于治疗与LRRK2受体相关的疾病，如帕金森病。
• [EN] 2-PHENYLAMINOPYRIMIDINE DERIVATIVES AS KINASE LRRK2 MODULATORS FOR THE TREATMENT OF PARKINSON'S DISEASE<br/>[FR] DÉRIVÉS 2-PHÉNYLAMINOPYRIMIDINES EN TANT QUE MODULATEURS DE KINASE LRRK2 POUR LE TRAITEMENT DE LA MALADIE DE PARKINSON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013079494A1

  公开（公告）日：2013-06-06

  Specific Compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein m, X, R, R2, R3, R, R6 and R7 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.

  具有以下化学式（I）的特定化合物：或其药用可接受的盐，其中m、X、R、R2、R3、R、R6和R7如本文所定义。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，如帕金森病。
• [EN] AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS<br/>[FR] DÉRIVÉS D'AMINOPYRIMIDINE AU TITRE DE MODULATEURS DE LRRK2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011151360A1

  公开（公告）日：2011-12-08

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R5, R6 and R7 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m，n，X，R1，R2，R3，R5，R6和R7的定义如本文所述。还披露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，如帕金森病。
• AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS
  申请人：Genentech, Inc.

  公开号：US20130157999A1

  公开（公告）日：2013-06-20

  Specific Compounds of formula I: or pharmaceutically acceptable salts thereof, wherein m, X, R 1 , R 2 , R 3 , R 5 , R 6 and R 7 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的特定化合物或其药学上可接受的盐，其中m，X，R1，R2，R3，R5，R6和R7的定义如本文所述。还揭示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，如帕金森病。
• Aminopyrimidine derivatives as LRRK2 inhibitors
  申请人：Baker-Glenn Charles

  公开号：US08354420B2

  公开（公告）日：2013-01-15

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n. X, R1, R2, R3, R5, R6 and R7 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.

  化合物I的公式为：或其药学上可接受的盐，其中m，n，X，R1，R2，R3，R5，R6和R7的定义如本文所述。还公开了制备该化合物的方法以及将该化合物用于治疗与LRRK2受体相关的疾病，如帕金森病的方法。