2-[1-[[2-(2-ethylbenzimidazol-1-yl)-6-morpholin-4-yl-7H-purin-8-yl]methyl]piperidin-4-yl]propan-2-ol | 1393804-18-6

• 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: 2-[1-[[2-(2-ethylbenzimidazol-1-yl)-6-morpholin-4-yl-7H-purin-8-yl]methyl]piperidin-4-yl]propan-2-ol
• CAS: 1393804-18-6
• 化学式: C₂₇H₃₆N₈O₂
• 分子量: 504.635
• InChiKey: WEZQILVZKONHBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-chloro-6-(morpholin-4-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 正丁基锂 、 四甲基乙二胺 、 caesium carbonate 、 对甲苯磺酸 、 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 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 2-[1-[[2-(2-ethylbenzimidazol-1-yl)-6-morpholin-4-yl-7H-purin-8-yl]methyl]piperidin-4-yl]propan-2-ol
  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

• [EN] BICYCLIC PYRIMIDINE PI3K INHIBITOR COMPOUNDS SELECTIVE FOR P110 DELTA, AND METHODS OF USE<br/>[FR] COMPOSÉS PYRIMIDINES BICYCLIQUES INHIBITEURS DE PI3K SÉLECTIFS POUR P110 DELTA, ET PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2010138589A1

  公开（公告）日：2010-12-02

  Formula (I) ((Ia) and (Ib)) compounds wherein (i) X1 is N and X2 is S, (ii) X1 is CR7 and X2 is S, (iii) X1 is N and X2 is NR2, or (iv) X1 is CR7 and X2 is O, including stereoisomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological, and cancer. Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式（I）（（Ia）和（Ib））化合物，其中（i）X1为N且X2为S，（ii）X1为CR7且X2为S，（iii）X1为N且X2为NR2，或（iv）X1为CR7且X2为O，包括其立体异构体，互变异构体，代谢物和药用可接受盐，用于抑制PI3K的δ异构体，并用于治疗由脂质激酶介导的疾病，如炎症，免疫和癌症。公开了使用公式（I）化合物进行体外，体内和体内诊断，预防或治疗哺乳动物细胞中的这类疾病或相关病理状况的方法。
• BICYCLIC PYRIMIDINE PI3K INHIBITOR COMPOUNDS SELECTIVE FOR P110 DELTA, AND METHODS OF USE
  申请人：Castanedo Georgette

  公开号：US20120178736A1

  公开（公告）日：2012-07-12

  Formula I (Ia and Ib) compounds wherein (i) X 1 is N and X 2 is S, (ii) X 1 is CR 7 and X 2 is S, (iii) X 1 is N and X 2 is NR 2 , or (iv) X 1 is CR 7 and X 2 is 0, including stereoisomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  Formula I（Ia和Ib）化合物中，其中（i）X1为N且X2为S，（ii）X1为CR7且X2为S，（iii）X1为N且X2为NR2，或（iv）X1为CR7且X2为0，包括立体异构体，互变异构体，代谢物和药学上可接受的盐，有用于抑制PI3K的δ异构体，并用于治疗由脂质激酶介导的疾病，例如炎症，免疫和癌症。公开了使用Formula I化合物的方法，用于哺乳动物细胞中的体外，体内和原位诊断，预防或治疗此类疾病或相关病理条件。
• US8173650B2
  申请人：——

  公开号：US8173650B2

  公开（公告）日：2012-05-08
• US8394796B2
  申请人：——

  公开号：US8394796B2

  公开（公告）日：2013-03-12
• 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.