2,3,4,5-tetramethylpyridine N-oxide | 848696-97-9

• 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: 2,3,4,5-tetramethylpyridine N-oxide
• 英文别名: 2,3,4,5-tetramethyl-pyridine1-oxide；tetramethylpyridine 1-oxide；tetramethylpyridine N-oxide；2,3,4,5-tetramethyl-1-oxidopyridin-1-ium
• CAS: 848696-97-9
• 化学式: C₉H₁₃NO
• 分子量: 151.208
• InChiKey: SUZSCKFKXYYYPD-UHFFFAOYSA-N

物化性质

• 沸点：
  334.0±11.0 °C(Predicted)
• 密度：
  0.98±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  25.5
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2,3,4,5-tetramethylpyridine N-oxide 在 四溴化碳 、 potassium carbonate 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-chloro-9-(3,4,5-trimethyl-pyridin-2-ylmethyl)-9H-purin-2-ylamine
  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 、 四氯化碳 、 甲苯 为溶剂， 反应 6.0h， 生成 2,3,4,5-tetramethylpyridine N-oxide
  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

• Pyridylacetic acid derivatives, their preparation, intermediates for
  申请人：BASF Aktiengesellschaft

  公开号：US05965587A1

  公开（公告）日：1999-10-12

  Pyridylacetic acid compounds of the formula I ##STR1## where X is NOCH.sub.3. CHOCH.sub.3, CHCH.sub.3 or CHCH.sub.2 CH.sub.3 ; and Y is oxygen or NR', and salts thereof, processes and intermediates for their preparation and compositions containing them which are used for controlling animal pests and fungi.

  化合物I的吡啶乙酸衍生物的公式为：##STR1## 其中X为NOCH.sub.3. CHOCH.sub.3, CHCH.sub.3或CHCH.sub.2 CH.sub.3; Y为氧或NR'，以及它们的盐，其制备的过程和中间体以及含有它们的组合物，用于控制动物害虫和真菌。
• 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。
• 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。
• New Compounds Useful for the Synthesis of S- and R-Omeprazole and a Process for Their Preparation
  申请人：von Unge Sverker

  公开号：US20090253911A1

  公开（公告）日：2009-10-08

  The present invention relates to an improved method for the synthesis of the (S)- or (R)-enantiomer of omeprazole, characterized in that 2-[[(4-X-3,5-dimethylpyridin-2-yl)methyl]thio]-5-methoxy-1H-benzimidazole or 2-[[(4-X-3,5-dimethyl-1-oxidopyridin-2-yl)methyl]thio]-5-methoxy-1H-benzimidazole, wherein X is a leaving group, is oxidized into the corresponding sulphoxide which is obtained as a crystalline compound. Recrystallisation of the thus obtained sulphoxide results in a compound of enhanced chemical and optical purity, which is subsequently transformed into the (S)- or (R)-enantiomer of omeprazole.

  本发明涉及一种改进的奥美拉唑（omeprazole）（S）或（R）对映体合成方法，其特征在于将2-[[(4-X-3,5-二甲基吡啶-2-基)甲基]硫基]-5-甲氧基-1H-苯并咪唑或2-[[(4-X-3,5-二甲基-1-氧代吡啶-2-基)甲基]硫基]-5-甲氧基-1H-苯并咪唑，其中X是一个离去基团，氧化为相应的磺酸氧化物，该磺酸氧化物以晶体化合物的形式获得。因此获得的磺酸氧化物再结晶，可得到化学和光学纯度更高的化合物，随后转化为奥美拉唑（S）或（R）对映体。
• Compounds Useful for the Synthesis of S- and R-Omeprazole and a Process for Their Preparation
  申请人：Fregler Christina

  公开号：US20080255199A1

  公开（公告）日：2008-10-16

  The present invention relates to an improved method for the synthesis of the (S)- or (R)-enantiomer of omeprazole, characterized in that 2-[[(4-X-3,5-dimethylpyridin-2-yl)methyl]thio]-5-methoxy-1H-benzimidazole or 2-[[(4-X-3,5-dimethyl-1-ox-idopyridin-2-yl) methyl]thio]-5-methoxy-1H-benzimidazole, wherein X is a leaving group, is oxidized into the corresponding sulphoxide which is obtained as a crystalline compound. Recrystallisation of the thus obtained sulphoxide results in a compound of enhanced chemical and optical purity, which is subsequently transformed into the (S)- or (R)-enantiomer of omeprazole.

  本发明涉及一种改进的奥美拉唑（omeprazole）（S）或（R）对映体合成方法，其特征在于将2-[[(4-X-3,5-二甲基吡啶-2-基)甲基]硫基]-5-甲氧基-1H-苯并咪唑或2-[[(4-X-3,5-二甲基-1-氧代吡啶-2-基)甲基]硫基]-5-甲氧基-1H-苯并咪唑（其中X是一个离去基团）氧化成相应的亚砜，该亚砜以结晶化合物的形式得到。因此获得的亚砜再结晶可得到化学和光学纯度提高的化合物，随后将其转化为（S）或（R）对映体的奥美拉唑。