4-chloro-1-(2-chloro-2-(4-chlorophenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidine | 1013930-74-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 4-chloro-1-(2-chloro-2-(4-chlorophenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 4-Chloro-1-[2-chloro-2-(4-chlorophenyl)ethyl]pyrazolo[3,4-d]pyrimidine
• CAS: 1013930-74-9
• 化学式: C₁₃H₉Cl₃N₄
• 分子量: 327.6
• InChiKey: XSXQKZTUDZLHIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-1-(2-chloro-2-(4-chlorophenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidine 、 3-氯苄胺 以 甲苯 为溶剂， 反应 48.0h， 以65%的产率得到1-[2-chloro-2-(4-chlorophenyl)ethyl]-N-[(3-chlorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  Structure-Based Optimization of Pyrazolo[3,4-d]pyrimidines as Abl Inhibitors and Antiproliferative Agents toward Human Leukemia Cell Lines

  摘要：

  Results from molecular docking calculations and Grid mapping laid the foundations for a structure-based optimization approach to improve the biological properties of pyrazolo-pyrimidine derivatives in terms of inhibition of Abl enzymatic activity and anti proliferative properties toward human leukemia cells. Insertion of halogen substituents with various substitution patterns, suggested by simulations, led to a significant improvement of leukemia cell growth inhibition and to an increase up to 1 order of magnitude of the affinity toward Abl.

  DOI：

  10.1021/jm701240c
• 作为产物：
  描述：

  4-氯-1H-吡唑并[3,4-d]嘧啶 在 sodium tetrahydroborate 、 四丁基氟化铵 、 三氯氧磷 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-chloro-1-(2-chloro-2-(4-chlorophenyl)ethyl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  合成生物学上相关的1,4-二取代的吡唑并[3,4- d ]嘧啶的另一种合成方法

  摘要：

  已经开发了一种通用的合成1，4-二取代的吡唑并[3，4- d ]嘧啶的方法。从商业上可获得的别嘌呤醇开始，TBAF介导的N1官能化和随后的C4亲核取代，在微波辅助或标准加热条件下，可得到具有潜在生物学意义的高度官能化的吡唑并[3,4- d ]嘧啶。

  DOI：

  10.1016/j.tetlet.2013.07.069

文献信息

• Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4-<i>d</i>]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study
  作者：Marco Radi、Elena Dreassi、Chiara Brullo、Emmanuele Crespan、Cristina Tintori、Vincenzo Bernardo、Massimo Valoti、Claudio Zamperini、Henry Daigl、Francesca Musumeci、Fabio Carraro、Antonella Naldini、Irene Filippi、Giovanni Maga、Silvia Schenone、Maurizio Botta

  DOI：10.1021/jm1012819

  日期：2011.4.28

  A family of dual Src/Abl inhibitors characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold was previously reported by us and proved to be active against several tumor cell lines. Among these compounds, a promising antileukemia lead (1) has been recently identified, but, unfortunately, it suffers from substandard pharmaceutical properties. Accordingly, an approach for the optimization of the lead 1 is described in the present work. A series of more soluble pyrazolo[3,4-d]pyrimidine derivatives were rationally designed and proved to maintain the dual Src/Abl activity of the lead. Selected compounds showed an interesting activity profile against three different leukemic cells also in hypoxic conditions, which are usually characterized by imatinib-resistance. Finally, in vitro ADME properties (PAMPA permeation, water solubility, microsomal stability) for the most promising inhibitors were also evaluated, thus allowing the identification of a few optimized analogues of lead 1 as promising antileukemia agents.
• Structure-Based Optimization of Pyrazolo[3,4-<i>d</i>]pyrimidines as Abl Inhibitors and Antiproliferative Agents toward Human Leukemia Cell Lines
  作者：Fabrizio Manetti、Chiara Brullo、Matteo Magnani、Francesca Mosci、Beatrice Chelli、Emmanuele Crespan、Silvia Schenone、Antonella Naldini、Olga Bruno、Maria Letizia Trincavelli、Giovanni Maga、Fabio Carraro、Claudia Martini、Francesco Bondavalli、Maurizio Botta

  DOI：10.1021/jm701240c

  日期：2008.3.13

  Results from molecular docking calculations and Grid mapping laid the foundations for a structure-based optimization approach to improve the biological properties of pyrazolo-pyrimidine derivatives in terms of inhibition of Abl enzymatic activity and anti proliferative properties toward human leukemia cells. Insertion of halogen substituents with various substitution patterns, suggested by simulations, led to a significant improvement of leukemia cell growth inhibition and to an increase up to 1 order of magnitude of the affinity toward Abl.
• An alternative synthetic approach for the synthesis of biologically relevant 1,4-disubstituted pyrazolo[3,4-d]pyrimidines
  作者：Marco Radi、Vincenzo Bernardo、Giulia Vignaroli、Annalaura Brai、Mariangela Biava、Silvia Schenone、Maurizio Botta

  DOI：10.1016/j.tetlet.2013.07.069

  日期：2013.9

  A versatile approach for the synthesis of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines has been developed. Starting from commercially available allopurinol, TBAF mediated N1-functionalization and subsequent C4 nucleophilic substitution, under microwave assisted- or standard heating conditions, granted access to highly functionalized pyrazolo[3,4-d]pyrimidines of potential biological interest.

  已经开发了一种通用的合成1，4-二取代的吡唑并[3，4- d ]嘧啶的方法。从商业上可获得的别嘌呤醇开始，TBAF介导的N1官能化和随后的C4亲核取代，在微波辅助或标准加热条件下，可得到具有潜在生物学意义的高度官能化的吡唑并[3,4- d ]嘧啶。