N-[1-(1,1-dioxothian-4-yl)azetidin-3-yl]-2-(2-ethylbenzimidazol-1-yl)-9-methyl-6-morpholin-4-ylpurin-8-amine | 1449776-82-2

• 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: N-[1-(1,1-dioxothian-4-yl)azetidin-3-yl]-2-(2-ethylbenzimidazol-1-yl)-9-methyl-6-morpholin-4-ylpurin-8-amine
• CAS: 1449776-82-2
• 化学式: C₂₇H₃₅N₉O₃S
• 分子量: 565.699
• InChiKey: PVAHRMVXBZGNMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  C₂₇H₃₅N₉O₃ 在 三乙酰氧基硼氢化钠 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 21.0h， 生成 N-[1-(1,1-dioxothian-4-yl)azetidin-3-yl]-2-(2-ethylbenzimidazol-1-yl)-9-methyl-6-morpholin-4-ylpurin-8-amine
  参考文献：
  名称：

  Identification of GNE-293, a potent and selective PI3Kδ inhibitor: Navigating in vitro genotoxicity while improving potency and selectivity

  摘要：

  In an effort to identify potent and isoform selective inhibitors of PI3K delta, GNE-293 (34) was identified. Inhibitor 2 was found to induce micronuclei formation in both the MNT and HCA in vitro assays. Compounds testing negative for genotoxicity were successfully identified through modifications of the 2-benzimidazole substituent and the methylene moiety to disrupt planarity. A variety of heteroatom linkers were explored to examine their effect on potency and isoform selectivity by restricting torsional angles to favor ligand interactions with PI3K delta's Trp760. These modifications also resulted in an improved in vivo pharmacokinetic profile. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.052

文献信息

• Identification of GNE-293, a potent and selective PI3Kδ inhibitor: Navigating in vitro genotoxicity while improving potency and selectivity
  作者：Brian S. Safina、Zachary K. Sweeney、Jun Li、Bryan K. Chan、Angelina Bisconte、Diane Carrera、Georgette Castanedo、Michael Flagella、Robert Heald、Cristina Lewis、Jeremy M. Murray、Jim Nonomiya、Jodie Pang、Steve Price、Karin Reif、Laurent Salphati、Eileen M. Seward、Binqing Wei、Daniel P. Sutherlin

  DOI：10.1016/j.bmcl.2013.06.052

  日期：2013.9

  In an effort to identify potent and isoform selective inhibitors of PI3K delta, GNE-293 (34) was identified. Inhibitor 2 was found to induce micronuclei formation in both the MNT and HCA in vitro assays. Compounds testing negative for genotoxicity were successfully identified through modifications of the 2-benzimidazole substituent and the methylene moiety to disrupt planarity. A variety of heteroatom linkers were explored to examine their effect on potency and isoform selectivity by restricting torsional angles to favor ligand interactions with PI3K delta's Trp760. These modifications also resulted in an improved in vivo pharmacokinetic profile. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.