4'-(cyclopropylmethyl)-N2'-neopentyl-N2-(pyridin-4-yl)-[4,5'-bipyrimidine]-2,2'-diamine | 1383716-45-7

• 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: 4'-(cyclopropylmethyl)-N2'-neopentyl-N2-(pyridin-4-yl)-[4,5'-bipyrimidine]-2,2'-diamine
• 英文别名: 4'-(cyclopropylmethyl)-N2'-neopentyl-N2-(pyridin-4-yl)-4,5'-bipyrimidine-2,2'-diamine；4-(cyclopropylmethyl)-N-(2,2-dimethylpropyl)-5-[2-(pyridin-4-ylamino)pyrimidin-4-yl]pyrimidin-2-amine
• CAS: 1383716-45-7
• 化学式: C₂₂H₂₇N₇
• 分子量: 389.503
• InChiKey: ORNLELIBWAZVOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-甲基-2-甲硫基嘧啶 在 potassium carbonate 、 间氯过氧苯甲酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲基叔丁基醚 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 4'-(cyclopropylmethyl)-N2'-neopentyl-N2-(pyridin-4-yl)-[4,5'-bipyrimidine]-2,2'-diamine
  参考文献：
  名称：

  Potent, Selective, and Orally Bioavailable Inhibitors of VPS34 Provide Chemical Tools to Modulate Autophagy in Vivo

  摘要：

  Autophagy is a dynamic process that regulates lysosomal-dependent degradation of cellular components. Until recently the study of autophagy has been hampered by the lack of reliable pharmacological tools, but selective inhibitors are now available to modulate the PI 3-kinase VPS34, which is required for autophagy. Here we describe the discovery of potent and selective VPS34 inhibitors, their pharmacokinetic (PK) properties, and ability to inhibit autophagy in cellular and mouse models.

  DOI：

  10.1021/acsmedchemlett.5b00335

文献信息

• [EN] BI-HETEROARYL COMPOUNDS AS VPS34 INHIBITORS<br/>[FR] COMPOSÉS BI-HÉTÉROARYLES EN TANT QU'INHIBITEURS DE VPS34
  申请人：NOVARTIS AG

  公开号：WO2012085815A1

  公开（公告）日：2012-06-28

  The present invention includes novel methods of treating a disease or disorder characterized by hyperactivity of Vps34, and compound as Vps34 inhibitors; particularly compounds of Formula I or a pharmaceutically acceptable salt thereof, as well as methods of treating a disease, disorder, or syndrome associated with Vps34 inhibition, particularly hyperproliferative diseases. The present invention also includes pharmaceutical compositions including compounds of formula I and pharmaceutically acceptable salts thereof.

  本发明涉及治疗由Vps34高活性特征的疾病或紊乱的新方法，以及作为Vps34抑制剂的化合物；特别是公式I的化合物或其药用盐，以及治疗与Vps34抑制相关的疾病、紊乱或综合症的方法，特别是高增殖性疾病。本发明还包括包括公式I化合物及其药用盐的药物组合物。
• BI-HETEROARYL COMPOUNDS AS VPS34 INHIBITORS
  申请人：Taracido Ivan Cornella

  公开号：US20140155402A1

  公开（公告）日：2014-06-05

  The present invention includes novel methods of treating a disease or disorder characterized by hyperactivity of Vps34, and compound as Vps34 inhibitors; particularly compounds of Formula I: or a pharmaceutically acceptable salt thereof, as well as methods of treating a disease, disorder, or syndrome associated with Vps34 inhibition, particularly hyperproliferative diseases. The present invention also includes pharmaceutical compositions including compounds of formula I and pharmaceutically acceptable salts thereof.

  本发明包括治疗由Vps34高活性所特征的疾病或障碍的新方法，以及作为Vps34抑制剂的化合物；特别是公式I的化合物：或其药学上可接受的盐，以及治疗与Vps34抑制相关的疾病、障碍或综合症的方法，特别是增殖过度性疾病的方法。本发明还包括包括公式I的化合物和其药学上可接受的盐的药物组合物。
• US8901147B2
  申请人：——

  公开号：US8901147B2

  公开（公告）日：2014-12-02
• Potent, Selective, and Orally Bioavailable Inhibitors of VPS34 Provide Chemical Tools to Modulate Autophagy <i>in Vivo</i>
  作者：Ayako Honda、Edmund Harrington、Ivan Cornella-Taracido、Pascal Furet、Mark S. Knapp、Meir Glick、Ellen Triantafellow、William E. Dowdle、Dmitri Wiedershain、Wieslawa Maniara、Christine Moore、Peter M. Finan、Lawrence G. Hamann、Brant Firestone、Leon O. Murphy、Erin P. Keaney

  DOI：10.1021/acsmedchemlett.5b00335

  日期：2016.1.14

  Autophagy is a dynamic process that regulates lysosomal-dependent degradation of cellular components. Until recently the study of autophagy has been hampered by the lack of reliable pharmacological tools, but selective inhibitors are now available to modulate the PI 3-kinase VPS34, which is required for autophagy. Here we describe the discovery of potent and selective VPS34 inhibitors, their pharmacokinetic (PK) properties, and ability to inhibit autophagy in cellular and mouse models.