(R)-8-(6-amino-5-((2,3-dichloropyridin-4-yl)thio)pyrazin-2-yl)-8-azaspiro[4.5]decan-1-amine

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (R)-8-(6-amino-5-((2,3-dichloropyridin-4-yl)thio)pyrazin-2-yl)-8-azaspiro[4.5]decan-1-amine
• 英文别名: (4R)-8-[6-amino-5-(2,3-dichloropyridin-4-yl)sulfanylpyrazin-2-yl]-8-azaspiro[4.5]decan-4-amine
• 化学式: C₁₈H₂₂Cl₂N₆S
• 分子量: 425.385
• InChiKey: PSKJCIJLNDJVDV-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (R)-N-((R)-8-(6-amino-5-((2,3-dichloropyridin-4-yl)thio)pyrazin-2-yl)-8-azaspiro[4.5]decan-1-yl)-2-methylpropane-2-sulfinamide 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 以7 mg的产率得到(R)-8-(6-amino-5-((2,3-dichloropyridin-4-yl)thio)pyrazin-2-yl)-8-azaspiro[4.5]decan-1-amine
  参考文献：
  名称：

  N-AZASPIROCYCLOALKANE SUBSTITUTED N-HETEROARYL COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF SHP2

  摘要：

  本发明涉及以下式I的化合物： 其中p、q、Y1、Y2、R1、R2a、R2b、R3a、R3b、R4a、R4b、R5a、R5b、R7和R8在本发明概要中有定义；能够抑制SHP2活性。本发明还提供了一种制备本发明化合物的方法，包括含有这些化合物的药物制剂以及在管理与SHP2异常活性相关的疾病或疾病的方法中使用这些化合物和组合物。

  公开号：

  US20170015680A1

文献信息

• [EN] N-AZASPIROCYCLOALKANE SUBSTITUTED N-HETEROARYL COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF SHP2<br/>[FR] COMPOSÉS N-HÉTÉROARYLE SUBSTITUÉS PAR UN N-AZASPIROCYCLOALCANE ET COMPOSITIONS POUR INHIBER L'ACTIVITÉ DE SHP2
  申请人：NOVARTIS AG

  公开号：WO2015107495A1

  公开（公告）日：2015-07-23

  The present invention relates to compounds of formula I: in which p, q, Y1, Y2, R1, R2a, R2b, R3a, R3b, R4a, R4b, R5a, R5b, R7 and R8 are defined in the Summary of the Invention; capable of inhibiting the activity of SHP2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with the aberrant activity of SHP2.

  本发明涉及式I的化合物：其中p、q、Y1、Y2、R1、R2a、R2b、R3a、R3b、R4a、R4b、R5a、R5b、R7和R8在发明摘要中有定义；能够抑制SHP2活性。本发明还提供了一种制备本发明化合物的方法，包括这种化合物的药物制剂以及在管理与SHP2异常活性相关的疾病或疾病中使用这种化合物和组合物的方法。
• N-azaspirocycloalkane substituted N-heteroaryl compounds and compositions for inhibiting the activity of SHP2
  申请人：NOVARTIS AG

  公开号：US10336774B2

  公开（公告）日：2019-07-02

  The present invention relates to compounds of formula I: in which p, q, Y1, Y2, R1, R2a, R2b, R3a, R3b, R4a, R4b, R5a, R5b, R7 and R8 are defined in the Summary of the Invention; capable of inhibiting the activity of SHP2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with the aberrant activity of SHP2.

  本发明涉及式 I 的化合物： 其中p、q、Y1、Y2、R1、R2a、R2b、R3a、R3b、R4a、R4b、R5a、R5b、R7和R8在发明概述中定义；能够抑制SHP2的活性。本发明进一步提供了制备本发明化合物的工艺、包含此类化合物的药物制剂以及使用此类化合物和组合物治疗与SHP2活性异常有关的疾病或失调的方法。
• SHP2 INHIBITORS AND METHODS OF USE THEREOF
  申请人：Research Development Foundation

  公开号：US20190231805A1

  公开（公告）日：2019-08-01

  Provided are methods for the treatment of insulin resistance and insulin receptor diseases with SHP2 inhibitors, such as allosteric inhibitors of SHP2 and RNAi or siRNA that target SHP2 expression. Compositions and methods for delivery of SHP2 inhibitors, such as liver-targeting liposomes or nanoparticles, are also provided.
• SHP2 INHIBITOR COMPOSITIONS AND METHODS FOR TREATING CANCER
  申请人：Revolution Medicines, Inc.

  公开号：US20200368238A1

  公开（公告）日：2020-11-26

  The present invention is directed to compositions and methods of treating or preventing diseases or disorders with inhibitors of SHP2, alone, and in combination with other therapeutic agents such as RAS pathway inhibitors (e.g., MEK inhibitors); methods of establishing appropriate treatment plans for subjects based upon the expression of one or more biomarker indicative of SHP2 inhibitor sensitivity; and methods of determining sensitivity to a SHP2 inhibitor based on a phosphorylation status of SHP2.
• SHP2 INHIBITOR COMPOSITIONS FOR USE IN TREATING CANCER
  申请人：Revolution Medicines, Inc.

  公开号：US20220031695A1

  公开（公告）日：2022-02-03

  The present disclosure provides methods of treating diseases or disorders using allosteric inhibitors of SHP2 and to methods and diagnostic tests for identifying subjects likely to respond to such allosteric inhibitors of SHP2. In particular, the present disclosure provides diagnostic and therapeutic uses related to certain Receptor Tyrosine Kinase (RTK) mutations that are indicative of sensitivity to allosteric SHP2 inhibitors.