1-(2-chloro-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one | 1006597-09-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-chloro-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one
• 英文别名: 1-(2-Chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidin-4-OL；1-(2-chlorophenyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one
• CAS: 1006597-09-6
• 化学式: C₁₁H₇ClN₄O
• mdl: MFCD11868161
• 分子量: 246.656
• InChiKey: OSQCFUBRJDCYLQ-UHFFFAOYSA-N

物化性质

• 沸点：
  455.2±51.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-chloro-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 在 劳森试剂 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-[1-(2-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]sulfanyl-N-(5-methylpyridin-2-yl)acetamide
  参考文献：
  名称：

  The discovery of a novel series of glucokinase activators based on a pyrazolopyrimidine scaffold

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.10.090
• 作为产物：
  描述：

  (2-氯苯基)-肼 在 硫酸 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 1-(2-chloro-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one
  参考文献：
  名称：

  The discovery of a novel series of glucokinase activators based on a pyrazolopyrimidine scaffold

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.10.090

文献信息

• 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。
• Aryl substituted purine analogues
  申请人：Bakthavatchalam Rajagopal

  公开号：US20070197559A1

  公开（公告）日：2007-08-23

  Aryl-substituted purine analogues are provided, of the formula: (I) wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies.

  本发明提供了芳基取代嘌呤类似物，其化学式为：(I)，其中变量如本文所述。这些化合物是配体，可用于调节体内或体外特定受体的活性，并且特别适用于治疗与人类、家养伴侣动物和家畜动物的病理性受体激活相关的疾病。本发明还提供了用于治疗此类疾病的制药组合物和方法，以及用于受体定位研究的这些配体的方法。
• Microwave-assisted protocols for the expedited synthesis of pyrazolo[1,5-a] and [3,4-d]pyrimidines
  作者：R. Nathan Daniels、Kwangho Kim、Evan P. Lebois、Hubert Muchalski、Mary Hughes、Craig W. Lindsley

  DOI：10.1016/j.tetlet.2007.11.054

  日期：2008.1

  General, high-yielding MAOS protocols for the expedited synthesis of functionalized pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyrimidines, as well as their pyrazole precursors, are described amenable to an iterative analogue library synthesis strategy for lead optimization. (c) 2007 Elsevier Ltd. All rights reserved.
• Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel mGluR4 positive allosteric modulators
  作者：Colleen M. Niswender、Evan P. Lebois、Qingwei Luo、Kwangho Kim、Hubert Muchalski、Huiyong Yin、P. Jeffrey Conn、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2008.08.087

  日期：2008.10

  This letter describes the synthesis and SAR, developed through an iterative analogue library approach, of an mGluR4 positive allosteric modulator lead based on a pyrazolo[3,4-d] pyrimidine scaffold. Despite tremendous therapeutic potential, Compound 7, VU0080421, and related congeners represent only a handful of mGluR4 positive allosteric modulators ever described. (C) 2008 Elsevier Ltd. All rights reserved.
• US8143263B2
  申请人：——

  公开号：US8143263B2

  公开（公告）日：2012-03-27