4'-(cyclopropylmethyl)-N2'-methyl-N2-(quinolin-3-yl)-[4,5'-bipyrimidine]-2,2'-diamine | 1383715-93-2

• 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'-methyl-N2-(quinolin-3-yl)-[4,5'-bipyrimidine]-2,2'-diamine
• 英文别名: N-[4-[4-(cyclopropylmethyl)-2-(methylamino)pyrimidin-5-yl]pyrimidin-2-yl]quinolin-3-amine
• CAS: 1383715-93-2
• 化学式: C₂₂H₂₁N₇
• 分子量: 383.456
• InChiKey: GCJHXHBCNCJIPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 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 24.0h， 生成 4'-(cyclopropylmethyl)-N2'-methyl-N2-(quinolin-3-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

• BI-HETEROARYL COMPOUNDS AS VPS34 INHIBITORS
  申请人：Novartis AG

  公开号：EP2655340B1

  公开（公告）日：2015-01-21
• 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.