4-(8-(chloromethyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholine

• 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-(8-(chloromethyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholine
• 英文别名: 8-Chloromethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine；4-[8-(chloromethyl)-2-(2-ethylbenzimidazol-1-yl)-9-methylpurin-6-yl]morpholine
• 化学式: C₂₀H₂₂ClN₇O
• 分子量: 411.894
• InChiKey: PLEFFCHNQZCHHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  73.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(8-(chloromethyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholine 在 potassium tert-butylate 、 sodium acetate 、 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.33h， 生成 4-cyclohexyl-1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperazin-2-one
  参考文献：
  名称：

  Identification of a potent and selective phosphatidylinositol 3-kinase δ inhibitor for the treatment of non-Hodgkin's lymphoma

  摘要：

  PI3Kδ has proved to be an effective target for anti-lymphoma drugs. However, the application of current approved PI3Kδ inhibitors has been greatly limited due to their specific immune-mediated toxicity and increased risk of infection, it is necessary to develop more PI3Kδ inhibitors with new scaffold. In this study, SAR study with respect to piperazinone-containing purine derivatives led to the discovery of a potent and selective PI3Kδ inhibitor, 4-(cyclobutanecarbonyl)-1-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperazin-2-one (WNY1613). WNY1613 exhibits good antiproliferative activity against a panel of non-Hodgkin's lymphoma (NHL) cell lines by inducing cancer cell apoptosis and inhibiting the phosphorylation of PI3K and MAPK downstream components. In addition, it can also prevent the tumor growth in both SU-DHL-6 and JEKO-1 xenograft models without observable toxicity. WNY1613 thus could be developed as a promising candidate for the treatment of NHL after subsequent extensive pharmacodynamics and pharmacokinetics investigation.

  DOI：

  10.1016/j.bioorg.2020.104344
• 作为产物：
  描述：

  4-(2-氯-9-甲基嘌呤-6-基)吗啉 在 甲醇 、 sodium tetrahydroborate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 正丁基锂 、 氯化亚砜 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 4-(8-(chloromethyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholine
  参考文献：
  名称：

  一种哌嗪酮取代物或其衍生物及其制备方法和应用、药物组合物

  摘要：

  一种哌嗪酮取代物或其衍生物及其制备方法和应用、药物组合物，属于抗肿瘤药物技术领域。本申请设计了一种哌嗪酮取代的杂环小分子化合物，此化合物对PI3Kδ展现出良好的亲和力，此化合物能在肿瘤细胞中下调PI3K通路活性，从而对PI3Kδ依赖的肿瘤展现良好的抑制活性，有望作为药物制剂的成分之一用于不同肿瘤的治疗。且本申请哌嗪酮取代物的制备方法简便，产率较高。

  公开号：

  CN112920199B

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。
• 一种哌嗪酮取代物或其衍生物及其制备方法和应用、药物组合物
  申请人：四川大学

  公开号：CN112920199B

  公开（公告）日：2023-02-03

  一种哌嗪酮取代物或其衍生物及其制备方法和应用、药物组合物，属于抗肿瘤药物技术领域。本申请设计了一种哌嗪酮取代的杂环小分子化合物，此化合物对PI3Kδ展现出良好的亲和力，此化合物能在肿瘤细胞中下调PI3K通路活性，从而对PI3Kδ依赖的肿瘤展现良好的抑制活性，有望作为药物制剂的成分之一用于不同肿瘤的治疗。且本申请哌嗪酮取代物的制备方法简便，产率较高。
• Bicyclic pyrimidine PI3K inhibitor compounds selective for P110 delta, and methods of use
  申请人：Genentech, Inc.

  公开号：US08173650B2

  公开（公告）日：2012-05-08

  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.

  Formula 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，包括立体异构体，互变异构体，代谢物和其药学上可接受的盐，对于抑制PI3K的δ异构体以及治疗由脂质激酶介导的疾病如炎症，免疫和癌症等有用。公开了使用Formula I化合物的方法，用于哺乳动物细胞中体外，体内和原位诊断，预防或治疗此类疾病或相关病理条件。
• 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