4-chloro-1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine | 650628-21-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-chloro-1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 4-chloro-1-(2-methoxyphenyl)pyrazolo[3,4-d]pyrimidine
• CAS: 650628-21-0
• 化学式: C₁₂H₉ClN₄O
• 分子量: 260.683
• InChiKey: BMTONOBXUHOYCV-UHFFFAOYSA-N

物化性质

• 沸点：
  369.6±42.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  52.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine 在 四氢吡咯 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 29.0h， 生成 isonicotinaldehyde [1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]hydrazone
  参考文献：
  名称：

  Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors

  摘要：

  A series of [1-aryl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]arylhydrazones were discovered as novel inhibitors glycogen synthase kinase-3 (GSK-3). Based on initial modeling a detailed SAR was constructed. Modification of the interior binding aryl ring (Art) determined this to be a tight binding region with little room for modification. As predicted from the model, a large variety of modifications could be incorporated into the hydrazone aryl ring. This work led to GSK-3 inhibitors in the low nano-molar range. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.02.036
• 作为产物：
  描述：

  2-甲氧基苯肼 在 三乙胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 4-chloro-1-(2-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  新型GLUT抑制剂的鉴定

  摘要：

  使用HTS将1 H-吡唑并[3,4- d ]嘧啶类化合物鉴定为促进葡萄糖转运蛋白1（GLUT1）的非常有效的抑制剂。建立了分子框架每个环系统的广泛结构-活性关系研究（SAR），揭示了必要的结构动机（即，邻甲氧基取代的苯，哌嗪和嘧啶）。对GLUT2的选择性非常好，并且最初的体外和体内药代动力学（PK）研究令人鼓舞。

  DOI：

  10.1016/j.bmcl.2016.02.050

文献信息

• [EN] PYRAZOLOPYRIMIDINES AS KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE SOUS FORME DE PYRAZOLOPYRIMIDINES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004009602A1

  公开（公告）日：2004-01-29

  The present invention relates generally to inhibitors of the kinases and more particularly to novel pyrazolopyrimidine compounds.

  本发明一般涉及激酶的抑制剂，更具体地涉及新型吡唑吡嘧啶化合物。
• THERAPEUTIC AGENTS 414
  申请人：BENNETT Stuart Norman Lile

  公开号：US20100093757A1

  公开（公告）日：2010-04-15

  A compound of Formula (I): is useful in the treatment or prevention of a disease or medical condition mediated through glucokinase (GLK or GK), leading to a decreased glucose threshold for insulin secretion.

  化合物Formula (I)在通过葡萄糖激酶（GLK或GK）介导的疾病或医疗状况的治疗或预防中很有用，导致胰岛素分泌的葡萄糖阈值降低。
• Synthesis of 1,4-Disubstituted Pyrazolo[3,4-d]pyrimidines from 4,6-Dichloropyrimidine-5-carboxaldehyde: Insights into Selectivity and Reactivity
  作者：Christie Morrill、Young-Choon Moon、Suresh Babu、Neil Almstead

  DOI：10.1055/s-0033-1338862

  日期：——

  Strategies for carrying out the reaction of 4,6-dichloropyrimidine-5-carboxaldehyde with both aromatic and aliphatic hydrazines to generate 1-substituted 4-chloropyrazolo[3,4-d]pyrimidines in a selective, high-yielding, and operationally simple manner are presented. For aromatic hydrazines, the reaction is performed at a high temperature in the absence of an external base. For aliphatic hydrazines, the reaction proceeds at room temperature in the presence of an external base. The observed selectivity and reactivity trends are rationalized through consideration of the proposed reaction mechanism. The 1-substituted 4-chloropyrazolo[3,4-d]pyrimidine products serve as versatile synthetic intermediates, through further functionalization of the 4-chloride moiety, enabling the rapid generation of a structurally diverse array of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines.
• The discovery of a novel series of glucokinase activators based on a pyrazolopyrimidine scaffold
  作者：Peter Bonn、D. Mikael Brink、Jonas Fägerhag、Ulrik Jurva、Graeme R. Robb、Volker Schnecke、Anette Svensson Henriksson、Michael J. Waring、Christer Westerlund

  DOI：10.1016/j.bmcl.2012.10.090

  日期：2012.12

  Glucokinase is a key enzyme in glucose homeostasis since it phosphorylates glucose to give glucose-6-phosphate, which is the first step in glycolysis. GK activators have been proven to lower blood-glucose, and therefore have potential as treatments for type 2 diabetes. Here the discovery of pyrazolopyrimidine GKAs is reported. An original singleton hit from a high-throughput screen with micromolar levels of potency was optimised to give compounds with nanomolar activities. Key steps in this success were the introduction of an extra side-chain, which increased potency, and changing the linking functionality from a thioether to an ether, which led to improved potency and lipophilic ligand efficiency. This also led to more stable compounds with improved profiles in biological assays. (C) 2012 Elsevier Ltd. All rights reserved.
• Selective Synthesis of 1-Substituted 4-Chloropyrazolo[3,4-<i>d</i>]pyrimidines
  作者：Suresh Babu、Christie Morrill、Neil G. Almstead、Young-Choon Moon

  DOI：10.1021/ol4005382

  日期：2013.4.19

  Strategies for carrying out the reaction of 4,6-dichloropyrimidine-5-carboxaldehyde with various hydrazines to generate 1-substituted 4-chloropyrazolo[3,4-d]pyrimidines in a selective and high-yielding manner are presented. For aromatic hydrazines, the reaction is performed in the absence of an external base, which promotes exclusive hydrazone formation. The hydrazones subsequently cyclize at an elevated temperature to form the desired pyrazolo[3,4-d]pyrimidine products. For aliphatic hydrazines, the reaction sequence proceeds as a single step in the presence of an external base.