4-[2-(2-Ethylbenzimidazol-1-yl)-9-methyl-8-[(4-methylsulfonylpiperazin-1-yl)methyl]purin-6-yl]morpholine | 1393804-20-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 4-[2-(2-Ethylbenzimidazol-1-yl)-9-methyl-8-[(4-methylsulfonylpiperazin-1-yl)methyl]purin-6-yl]morpholine
• 英文别名: 4-[2-(2-ethylbenzimidazol-1-yl)-9-methyl-8-[(4-methylsulfonylpiperazin-1-yl)methyl]purin-6-yl]morpholine
• CAS: 1393804-20-0
• 化学式: C₂₅H₃₃N₉O₃S
• 分子量: 539.662
• InChiKey: ZNSBCWQNPXMYDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  123
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-(2-氯-9-甲基嘌呤-6-基)吗啉 在 sodium tetrahydroborate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 正丁基锂 、 四甲基乙二胺 、 三溴化磷 、 caesium carbonate 、 N,N-二异丙基乙胺 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 4-[2-(2-Ethylbenzimidazol-1-yl)-9-methyl-8-[(4-methylsulfonylpiperazin-1-yl)methyl]purin-6-yl]morpholine
  参考文献：
  名称：

  Potent and Highly Selective Benzimidazole Inhibitors of PI3-Kinase Delta

  摘要：

  Inhibition of PI3K delta is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective benzimidazole-based inhibitors of PI3K delta. These inhibitors do not occupy the selectivity pocket between Trp760 and Met752 that is induced by other families of PI3K delta inhibitors. Instead, the selectivity of the compounds for inhibition of PI3K delta relative to other PI3K isoforms appears to be due primarily to the strong interactions these inhibitors are able to make with Trp760 in the PI3K delta binding pocket. The pharmacokinetic properties and the ability of compound 5 to inhibit the function of B-cells in vivo are described.

  DOI：

  10.1021/jm300717c

文献信息

• Potent and Highly Selective Benzimidazole Inhibitors of PI3-Kinase Delta
  作者：Jeremy M. Murray、Zachary K. Sweeney、Bryan K. Chan、Mercedesz Balazs、Erin Bradley、Georgette Castanedo、Christine Chabot、David Chantry、Michael Flagella、David M. Goldstein、Rama Kondru、John Lesnick、Jun Li、Matthew C. Lucas、Jim Nonomiya、Jodie Pang、Stephen Price、Laurent Salphati、Brian Safina、Pascal P. A. Savy、Eileen M. Seward、Mark Ultsch、Daniel P. Sutherlin

  DOI：10.1021/jm300717c

  日期：2012.9.13

  Inhibition of PI3K delta is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective benzimidazole-based inhibitors of PI3K delta. These inhibitors do not occupy the selectivity pocket between Trp760 and Met752 that is induced by other families of PI3K delta inhibitors. Instead, the selectivity of the compounds for inhibition of PI3K delta relative to other PI3K isoforms appears to be due primarily to the strong interactions these inhibitors are able to make with Trp760 in the PI3K delta binding pocket. The pharmacokinetic properties and the ability of compound 5 to inhibit the function of B-cells in vivo are described.