(3,4,5-trimethylpyridin-2yl)methanol | 848696-99-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (3,4,5-trimethylpyridin-2yl)methanol
• 英文别名: (3,4,5-trimethyl-pyridin-2-yl)-methanol；3,4,5-Trimethyl-2-pyridinemethanol；(3,4,5-trimethylpyridin-2-yl)methanol
• CAS: 848696-99-1
• 化学式: C₉H₁₃NO
• 分子量: 151.208
• InChiKey: LHGBWURDKWZWLB-UHFFFAOYSA-N

物化性质

• 沸点：
  290.2±35.0 °C(Predicted)
• 密度：
  1.040±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3,4,5-trimethylpyridin-2yl)methanol 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 生成 2-bromomethyl-3,4,5-trimethylpyridine
  参考文献：
  名称：

  Rationally Designed High-Affinity 2-Amino-6-halopurine Heat Shock Protein 90 Inhibitors That Exhibit Potent Antitumor Activity

  摘要：

  Heat shock protein 90 (Hsp90) is a molecular chaperone protein implicated in stabilizing the conformation and maintaining the function of many cell-signaling proteins. Many oncogenic proteins are more dependent on Hsp90 in maintaining their conformation, stability, and maturation than their normal counterparts. Furthermore, recent data show that Hsp90 exists in an activated form in malignant cells but in a latent inactive form in normal tissues, suggesting that inhibitors selective for the activated form could provide a high therapeutic index. Hence, Hsp90 is emerging as an exciting new target for the treatment of cancer. We now report on a novel series of 2-amino-6-halopurine Hsp90 inhibitors exemplified by 2-amino-6-chloro-9-(4-iodo-3,5-dimethylpyridin-2-ylmethyl)purine (30). These highly potent inhibitors (IC50 of 30 = 0.009 mu M in a HER-2 degradation assay) also display excellent antiproliferative activity against various tumor cell lines (IC50 of 30 = 0.03 mu M in MCF7 cells). Moreover, this class of inhibitors shows higher affinity for the activated form of Hsp90 compared to our earlier 8-sulfanylpurine Hsp90 inhibitor series. When administered orally to mice, these compounds exhibited potent tumor growth inhibition (> 80%) in an N87 xenograft model, similar to that observed with 17-allylamino-17-desmethoxygeldanamycin (17-AAG), which is a compound currently in phase I/II clinical trials.

  DOI：

  10.1021/jm050752+
• 作为产物：
  描述：

  2,3,5-三甲基吡啶 1-氧化物 在 四(三苯基膦)钯 溴 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 甲苯 为溶剂， 反应 6.0h， 生成 (3,4,5-trimethylpyridin-2yl)methanol
  参考文献：
  名称：

  Rationally Designed High-Affinity 2-Amino-6-halopurine Heat Shock Protein 90 Inhibitors That Exhibit Potent Antitumor Activity

  摘要：

  Heat shock protein 90 (Hsp90) is a molecular chaperone protein implicated in stabilizing the conformation and maintaining the function of many cell-signaling proteins. Many oncogenic proteins are more dependent on Hsp90 in maintaining their conformation, stability, and maturation than their normal counterparts. Furthermore, recent data show that Hsp90 exists in an activated form in malignant cells but in a latent inactive form in normal tissues, suggesting that inhibitors selective for the activated form could provide a high therapeutic index. Hence, Hsp90 is emerging as an exciting new target for the treatment of cancer. We now report on a novel series of 2-amino-6-halopurine Hsp90 inhibitors exemplified by 2-amino-6-chloro-9-(4-iodo-3,5-dimethylpyridin-2-ylmethyl)purine (30). These highly potent inhibitors (IC50 of 30 = 0.009 mu M in a HER-2 degradation assay) also display excellent antiproliferative activity against various tumor cell lines (IC50 of 30 = 0.03 mu M in MCF7 cells). Moreover, this class of inhibitors shows higher affinity for the activated form of Hsp90 compared to our earlier 8-sulfanylpurine Hsp90 inhibitor series. When administered orally to mice, these compounds exhibited potent tumor growth inhibition (> 80%) in an N87 xenograft model, similar to that observed with 17-allylamino-17-desmethoxygeldanamycin (17-AAG), which is a compound currently in phase I/II clinical trials.

  DOI：

  10.1021/jm050752+

文献信息

• RADIOLABELLED PDE10 LIGANDS
  申请人：Andrés-Gil José Ignacio

  公开号：US20120213703A1

  公开（公告）日：2012-08-23

  The present invention relates to novel, selective, radiolabelled PDE10 ligands which are useful for imaging and quantifying the PDE10A enzyme in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo.

  本发明涉及新型的、选择性的、放射性标记的PDE10配体，这些配体可用于通过正电子发射断层扫描（PET）对组织中的PDE10A酶进行成像和定量。该发明还涉及包含这些化合物的组合物、制备这些化合物和组合物的方法，以及将这些化合物和组合物用于在体外或体内成像组织、细胞或宿主的应用。
• Synthesis, In Vivo Occupancy, and Radiolabeling of Potent Phosphodiesterase Subtype-10 Inhibitors as Candidates for Positron Emission Tomography Imaging
  作者：José-Ignacio Andrés、Meri De Angelis、Jesús Alcázar、Laura Iturrino、Xavier Langlois、Stefanie Dedeurwaerdere、Ilse Lenaerts、Greet Vanhoof、Sofie Celen、Guy Bormans

  DOI：10.1021/jm200536d

  日期：2011.8.25

  for in vivo imaging using positron emission tomography (PET). We now describe the synthesis and biological evaluation of a series of related pyridinyl analogues that exhibit high potency and selectivity as PDE10A inhibitors. The most interesting compounds were injected in rats to measure their levels of PDE10A occupancy through an in vivo occupancy assay. The 3,5-dimethylpyridine derivative 3 and the

  我们最近报道了磷酸二酯酶10A（PDE10A）抑制剂2- [4- [1-（2- [ 18 [ ] F]氟乙基）-4-吡啶-4-4-基-1 H-吡唑-3-基]-苯氧基甲基]-喹啉（[ 18 F] 1a）是使用正电子发射断层扫描（PET）进行体内成像的有前途的候选物。现在，我们描述了一系列相关的吡啶基类似物的合成和生物学评估，这些吡啶基类似物作为PDE10A抑制剂具有很高的效力和选择性。将最有趣的化合物注射到大鼠中，以通过体内占有率测定法测量其PDE10A占有率水平。3,5-二甲基吡啶衍生物3和5-甲氧基吡啶衍生物4的可比性与1a。因为这些衍生物显示出较低的体外活性，并且比1a的亲脂性略低，所以我们假设它们可以表现为更好的PET成像配体。放射性合成化合物[ 18 F] 3，[ 18 F] 4和[ 11 C] 4并在大鼠中进行生物分布研究，作为在脑中对PDE10A进行体内成像的候选PET放射性配体进行初步评估。
• 2-Aminopurine analogs having HSP90-inhibiting activity
  申请人：Kasibhatla Rao Srinivas

  公开号：US20050113340A1

  公开（公告）日：2005-05-26

  2-Aminopurine analogs are described and demonstrated or predicted to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents in the treatment and prevention of various HSP90 mediated disorders, e.g., proliferative disorders. Method of synthesis and use of such compounds are also described and claimed.

  本文描述了2-氨基嘌呤类似物，并展示或预测其作为热休克蛋白90（HSP90）抑制剂，在治疗和预防各种HSP90介导的疾病，例如增殖性疾病方面具有实用性。还描述和声明了这些化合物的合成方法和使用方法。
• [EN] RADIOLABELLED PDE10 LIGANDS<br/>[FR] LIGANDS PDE10 RADIOMARQUÉS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2011051324A1

  公开（公告）日：2011-05-05

  The present invention relates to novel, selective, radio labelled PDE10 ligands which are useful for imaging and quantifying the PDE10A enzyme in tissues, using positron- emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo.

  本发明涉及一种新型、选择性、放射性标记的PDE10配体，其可用于使用正电子发射断层扫描（PET）成像和定量组织中的PDE10A酶。本发明还涉及包含这种化合物的组合物，制备这种化合物和组合物的过程，以及使用这种化合物和组合物在体外或体内成像组织、细胞或宿主。
• 2-aminopurine analogs having HSP90-inhibiting activity
  申请人：Conforma Therapeutics Corporation

  公开号：US07138401B2

  公开（公告）日：2006-11-21

  2-Aminopurine analogs are described and demonstrated or predicted to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents in the treatment and prevention of various HSP90 mediated disorders, e.g., proliferative disorders. Method of synthesis and use of such compounds are also described and claimed.

  描述了2-氨基嘌呤类似物，并证明或预测其在治疗和预防各种HSP90介导的疾病，例如增殖性疾病中作为热休克蛋白90（HSP90）抑制剂的效用。还描述和声明了这些化合物的合成方法和用途。