methyl 6-chloronicotinate 1-oxide | 677763-16-5

• 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: methyl 6-chloronicotinate 1-oxide
• 英文别名: methyl 6-chloropyridine-3-carboxylate-1-oxide；methyl 6-chloronicotinate N-oxide；methyl 6-chloro-1-oxidopyridin-1-ium-3-carboxylate
• CAS: 677763-16-5
• 化学式: C₇H₆ClNO₃
• 分子量: 187.583
• InChiKey: LGFJPMKMBADHJV-UHFFFAOYSA-N

物化性质

• 沸点：
  366.7±22.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 6-chloronicotinate 1-oxide 在 甲醇 、 水 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸酐 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 55.0h， 生成 2-(1-(benzyloxy)-6-oxo-1,6-dihydropyridine-3-carboxamido)-2-phenylacetic acid
  参考文献：
  名称：

  THERAPEUTIC METHODS AND COMBINATIONS

  摘要：

  本发明涉及含有取代的1-羟基吡啶-2（1H）-硫酮或其药学上可接受的盐和抗菌剂的组合物。还公开了包括给予取代的1-羟基吡啶-2（1H）-硫酮或其药学上可接受的盐和抗菌剂的治疗方法。

  公开号：

  US20180369217A1
• 作为产物：
  描述：

  6-氯烟酸甲酯 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以67%的产率得到methyl 6-chloronicotinate 1-oxide
  参考文献：
  名称：

  通过合理的针对性重用方法发现基于碳酸酐酶抑制剂的新型潜在抗感染化合物

  摘要：

  在学术界，化合物回收代表了另一种药物发现策略，可从内部可用的化合物库中识别新的药物靶标。在此，我们报告了一种合理的基于目标药物的重新定位方法的应用，该方法可为我们内部的化合物收集找到多种应用。碳酸酐酶（CA，EC 4.2.1.1）金属酶超家族被确定为我们化合物的潜在目标。彻底验证的对接筛选方案与针对各种CA家族和同工型的体外测定相结合，使我们能够鉴定出两种史无前例的化学型作为CA抑制剂。

  DOI：

  10.1002/cmdc.201600180

文献信息

• Arylation, Alkenylation, and Alkylation of 2-Halopyridine <i>N</i>-Oxides with Grignard Reagents: A Solution to the Problem of C2/C6 Regioselective Functionalization of Pyridine Derivatives
  作者：Song Zhang、Lian-Yan Liao、Fang Zhang、Xin-Fang Duan

  DOI：10.1021/jo302511s

  日期：2013.3.15

  alkenylation, and alkylation of functionalized 2-halopyridine N-oxides with various Grignard reagents was developed. It represented a highly efficient and selective C–H bond functionalization of pyridine derivatives in the presence of reactive C–Cl or C–Br bonds. Using Cl or Br as a blocking group, C2/C6 site-controllable functionalization of pyridine derivatives has been achieved. Various pyridine compounds

  开发了各种格氏试剂的简便芳基化，烯基化和烷基化的功能化的2-卤代吡啶N-氧化物。它代表了在存在反应性C–Cl或C–Br键的情况下吡啶衍生物的高效C–H键选择性官能化。使用Cl或Br作为封闭基团，已经实现了吡啶衍生物的C2 / C6位点可控的官能化。如Onychine，dielsine和PARP-1抑制剂GPI 16539的总合成所示，可以制备各种吡啶化合物。
• N-substituted-2-oxodihydropyridine derivatives
  申请人：——

  公开号：US20040072874A1

  公开（公告）日：2004-04-15

  A compound of the formula (I): 1 (wherein Ar 1 and Ar 2 are independently aryl or heteroaryl, any of which is optionally substituted by a substituent selected from the group consisting of cyano, halogen, nitro, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, cyclo-lower alkyl, cyclo (lower alkyl)-lower alkyl, lower alkenyl, lower alkylamino, di-lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, arylsulfonylamino, hydroxy, lower alkoxy, halo-lower alkoxy, aryloxy, heteroaryloxy, lower alkylthio, carboxyl, formyl, lower alkanoyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, lower alkylsulfonyl, arylsulfonyl, aryl and heteroaryl; R 1 and R 2 are independently lower alkyl, cyclo-lower alkyl, cyclo(lower alkyl)-lower alkyl or lower alkoxy, any of which is optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl; R 3 , R 4 and R 5 are independently hydrogen, cyano, halogen or hydroxy, or lower alkyl, lower alkoxy or lower alkylthio, the last three groups being optionally substituted by a substituent selected from the group consisting of halogen, lower alkylamino, di-lower alkylamino, lower alkanoylamino, hydroxy, lower alkoxy, formyl, lower alkoxycarbonyl, lower alkylcarbamoyl and di-lower alkylcarbamoyl), or a salt or ester thereof is useful as a neuropeptide Y receptor antagonist agent and is also useful as an agent for the treatment of bulimia, obesity or diabetes.

  化合物的结构式(I):1（其中Ar1和Ar2分别独立地为芳基或杂环芳基，任何一个可以选择性地被来自以下组的取代基取代，该组包括氰基、卤素、硝基、较低烷基、卤代较低烷基、羟基较低烷基、环较低烷基、环（较低烷基）-较低烷基、较低烯基、较低烷基氨基、二较低烷基氨基、较低烷酰氨基、较低烷基磺酰氨基、芳基磺酰氨基、羟基、较低烷氧基、卤代较低烷氧基、芳氧基、杂环芳氧基、较低烷硫基、羧基、甲酰基、较低烷酰基、较低烷氧羰基、氨基甲酰基、较低烷基氨基甲酰基、二较低烷基氨基甲酰基、较低烷基磺酰基、芳基磺酰基、芳基和杂环芳基；R1和R2独立地为较低烷基、环较低烷基、环（较低烷基）-较低烷基或较低烷氧基，任何一个可以选择性地被来自以下组的取代基取代，该组包括卤素、较低烷基氨基、二较低烷基氨基、较低烷酰氨基、羟基、较低烷氧基、甲酰基、较低烷氧羰基、较低烷基氨基甲酰基和二较低烷基氨基甲酰基；R3、R4和R5独立地为氢、氰基、卤素或羟基，或较低烷基、较低烷氧基或较低烷硫基，最后三个基可以选择性地被来自以下组的取代基取代，该组包括卤素、较低烷基氨基、二较低烷基氨基、较低烷酰氨基、羟基、较低烷氧基、甲酰基、较低烷氧羰基、较低烷基氨基甲酰基和二较低烷基氨基甲酰基），或其盐或酯是一种神经肽Y受体拮抗剂药物，也是一种治疗厌食症、肥胖症或糖尿病的药物。
• TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS
  申请人：Biswas Kaustav

  公开号：US20130157996A1

  公开（公告）日：2013-06-20

  Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物可用作TRPM8的拮抗剂。这些化合物在治疗许多TRPM8介导的疾病和病症方面非常有用，并可用于制备用于治疗此类疾病和病症的药物和制剂。此类疾病的示例包括但不限于偏头痛和神经病性疼痛。公式I的化合物具有以下结构：其中变量的定义在此提供。
• TRPM8 antagonists and their use in treatments
  申请人：Chen Jian J.

  公开号：US08710043B2

  公开（公告）日：2014-04-29

  Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  式I的化合物可作为TRPM8拮抗剂使用。这些化合物可用于治疗多种TRPM8介导的疾病和症状，并可用于制备治疗此类疾病和症状的药物和制剂。这些疾病的例子包括但不限于偏头痛和神经病性疼痛。式I的化合物具有以下结构：其中变量的定义在此提供。
• 2-Aminonicotinic Acid 1-Oxides Are Chemically Stable Inhibitors of Quinolinic Acid Synthesis in the Mammalian Brain: A Step toward New Antiexcitotoxic Agents
  作者：Gian Paolo Vallerini、Laura Amori、Claudia Beato、Margarita Tararina、Xiao-Dan Wang、Robert Schwarcz、Gabriele Costantino

  DOI：10.1021/jm401249c

  日期：2013.12.12

  3-Hydroxyanthranilic acid 3,4-dioxygenase (3-HAO) is the enzyme responsible for the production of the neurotoxic tryptophan metabolite quinolinic acid (QUIN). Elevated brain levels of QUIN are observed in several neurodegenerative diseases, but pharmacological investigation on its role in the pathogenesis of these conditions is difficult because only one class of substrate-analogue 3-HAO inhibitors, with poor chemical stability, has been reported so far. Here we describe the design, synthesis, and biological evaluation of a novel class of chemically stable inhibitors based on the 2-aminonicotinic acid 1-oxide nucleus. After the preliminary in vitro evaluation of newly synthesized compounds using brain tissue homogenate, we selected the most active inhibitor and showed its ability to acutely reduce the production of QUIN in the rat brain in vivo. These findings provide a novel pharmacological tool for the study of the mechanisms underlying the onset and propagation of neurodegenerative diseases.