2-chloro-9-isopropyl-N-phenyl-9H-purin-6-amine | 203436-33-3

• 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-chloro-9-isopropyl-N-phenyl-9H-purin-6-amine
• 英文别名: 2-chloro-6-anilino-9-isopropylpurine；2-chloro-N-phenyl-9-propan-2-ylpurin-6-amine
• CAS: 203436-33-3
• 化学式: C₁₄H₁₄ClN₅
• 分子量: 287.752
• InChiKey: RBHBZMKUZOEORT-UHFFFAOYSA-N

物化性质

• 沸点：
  443.5±50.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-9-isopropyl-N-phenyl-9H-purin-6-amine 在 水 、 caesium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 1.17h， 生成
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer

  摘要：

  In the current study, we have designed and synthesized a series of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent kinase2 (CDK2) dual inhibitors by integrating purine-based pharmacophore into the recognition cap group of CS055. The representative compound 14d with excellent anti-proliferative activities towards five solid cancer cells, showed potent inhibitory activities against HDAC1, HDAC2 and CDK2 with IC50 values of 70.7 nM, 23.1 nM and 0.80 mu M, respectively. Besides, compound 14d could effectively block the cell cycle in the G2/M phase and induce apoptosis, which might be related to increasing intracellular ROS levels. Importantly, compound 14d exhibited desirable pharmacokinetic (PK) properties with the intraperitoneal bioavailability of 50.8% in ICR mice, and potent in vivo antitumor activity in the HCT116 xenograft model. Therefore, compound 14d could be considered as a promising lead compound for the development of multitargeting anticancer agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112322
• 作为产物：
  描述：

  2,6-二氯嘌呤 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 生成 2-chloro-9-isopropyl-N-phenyl-9H-purin-6-amine
  参考文献：
  名称：

  Synthesis and activity of 2,6,9-trisubstituted purines

  摘要：

  The preparation of a series of 2,6,9-trisubstituted purines and the structure-activity data for the inhibition of cyclin dependent kinase, CDK2 are presented. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)10076-2

文献信息

• 嘧啶并五元杂环类化合物及其作为突变型IDH2抑制剂的用途
  申请人：上海仕谱生物科技有限公司

  公开号：CN111825674A

  公开（公告）日：2020-10-27

  本发明涉及一种嘧啶并五元杂环类化合物及其作为突变型IDH2抑制剂的用途，具体地，本发明公开了一种可作为突变型IDH2抑制剂的嘧啶并五元杂环类化合物、或其立体异构体或互变异构体、或药学上可接受的盐、水合物或溶剂化物。本发明还涉及包含上述化合物的药物组合物及其用于制备预防和/或治疗突变型IDH2介导的疾病的药物的用途。
• Purine inhibitors of cyclin dependent kinase 2
  申请人：CV Therapeutics, Incorporation

  公开号：US05866702A1

  公开（公告）日：1999-02-02

  A 2,6,9-trisubstituted purine composition having the following formula: ##STR1## where X is a amino, oxo, thio, of sulfone moiety, R.sub.1 is a lower alkyl, substituted lower alkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, heterocycle, hetaryl, substituted hetaryl, aralkyl, heteroaralkyl, heteroalkyl, alkyl alkenyl, alkyl alkynyl, alkyl cycloalkyl, or alkyl cycloheteroalkyl, each having from 1 to 20 carbon atoms; R.sub.2 is hydrogen, lower alkyl, substituted lower alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocycle, hetaryl, substituted hetaryl, aralkyl, heteroaralkyl, heteroalkyl, alkyl alkenyl, alkyl alkynyl, alkyl cycloalkyl, or alkyl cycloheteroalkyl; and R.sub.3 is halogen, hydroxyl, thio, alkoxy, alkylthio, lower alkyl, --NR.sub.4 R.sub.5 or a component having the formula: ##STR2## wherein when R.sub.3 is 2-hydroxyethylamino and R.sub.2 is methyl, R.sub.1 -X is not amino, 3-methyl-2-butenylamino, benzylamino, or m-hydroxybenzyl-amino, when R.sub.3 is 2-hydroxyethylamino and R.sub.2 is isopropyl, R.sub.1 -X is not benzylamino, m-hydroxybenzylamino, or 3-methylbutylamino, when R.sub.3 is 2-hydroxyethylamino and R.sub.2 is 2-hydroxyethyl, R.sub.1 -X is not benzylamino and when R.sub.3 is selected from the group consisting of 2-propanol-2-methylamino and 2-dimethylaminoethylamino and R.sub.2 is methyl, then R.sub.1 -X is not benzylamino.

  具有以下公式的2,6,9-三取代嘌呤组成物：##STR1## 其中X是氨基，氧代基，硫代基或磺酰基，R.sub.1是低碳链烷基，取代低碳链烷基，环烷基，取代环烷基，环杂烷基，取代环杂烷基，芳基，取代芳基，杂环，杂芳基，取代杂芳基，芳基烷基，杂芳基烷基，杂基烷基，烷基烯烃基，烷基炔烃基，烷基环烷基或烷基环杂烷基，每个都有1到20个碳原子；R.sub.2是氢，低碳链烷基，取代低碳链烷基，环烷基，取代环烷基，芳基，取代芳基，杂环，杂芳基，取代杂芳基，芳基烷基，杂芳基烷基，杂基烷基，烷基烯烃基，烷基炔烃基，烷基环烷基或烷基环杂烷基；R.sub.3是卤素，羟基，硫代基，烷氧基，烷基硫代基，低碳链烷基，--NR.sub.4 R.sub.5或具有以下公式的组分：##STR2## 当R.sub.3是2-羟乙基氨基且R.sub.2是甲基时，R.sub.1 -X不是氨基，3-甲基-2-丁烯基氨基，苄基氨基或m-羟基苄基氨基；当R.sub.3是2-羟乙基氨基且R.sub.2是异丙基时，R.sub.1 -X不是苄基氨基，m-羟基苄基氨基或3-甲基丁基氨基；当R.sub.3是2-羟乙基氨基且R.sub.2是2-羟乙基时，R.sub.1 -X不是苄基氨基；当R.sub.3选自由2-异丙醇基-2-甲基氨基和2-二甲基氨基乙基氨基且R.sub.2是甲基时，R.sub.1 -X不是苄基氨基。
• Purine inhibitors of cyclin dependent kinase 2 and IkappaB-alpha
  申请人：Lum T. Robert

  公开号：US20050080261A1

  公开（公告）日：2005-04-14

  Compounds of the following formula are provided: In the Formula (I), R 1 is —X—R 1 ′; in which R 1 ′ is optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl, and X is —NH—. R 2 is lower alkyl optionally substituted with one, two or three groups chosen from hydroxy, lower alkoxy, and halogen. And R 3 is —NR 4 R 5 ; in which R 4 is hydrogen and R 5 is lower alkyl substituted with amino; or (ii) R 4 and R 5 are both lower alkyl optionally substituted with one, two or three groups chosen from hydroxy and amino. It is to be understood that R 1 ′ is not cyclohexylmethyl, phenyl, substituted phenyl, benzyl, phenylethyl, or m-hydroxybenzyl. The compounds inhibit CDK-2 activity and are useful for treating disorders characterized by undesirable cell proliferation.

  提供以下公式的化合物：在公式（I）中，R1为—X—R1′；其中R1′为可选择取代的低烷基、可选择取代的芳基、可选择取代的杂芳基或可选择取代的杂环烷基，X为—NH—。R2为低烷基，可选择取代一个、两个或三个羟基、低烷氧基或卤素基。R3为—NR4R5；其中R4为氢，R5为取代氨基的低烷基；或（ii）R4和R5均为低烷基，可选择取代一个、两个或三个羟基和氨基。应理解R1′不是环己基甲基、苯基、取代苯基、苄基、苯乙基或间羟基苄基。这些化合物能够抑制CDK-2活性，并用于治疗具有不良细胞增殖特征的疾病。
• Purine inhibitors of cyclin dependent kinase 2 & IkappaBalpha
  申请人：CV Therapeutics, Inc.

  公开号：US20020032327A1

  公开（公告）日：2002-03-14

  A 2,6,9-trisubstituted purine composition that is useful for inhibiting cell proliferative disorders and as an antifungal agent.

  一种2,6,9-三取代嘌呤组合物，可用于抑制细胞增殖性疾病和作为抗真菌剂。
• Purine inhibitors of cyclin dependent kinase 2 & IkBa
  申请人：——

  公开号：US20020035252A1

  公开（公告）日：2002-03-21

  A 2,6,9-trisubstituted purine composition that is useful for inhibiting cell proliferative disorders and as an antifungal agent.

  一种2,6,9-三取代嘌呤组合物，可用于抑制细胞增殖性疾病和作为抗真菌剂。