N-(3-chloro-4-aminophenyl)-2-picolinamide | 1308655-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-chloro-4-aminophenyl)-2-picolinamide
• 英文别名: N-(4-amino-3-chlorophenyl)picolinamide；N-(4-amino-3-chlorophenyl)pyridine-2-carboxamide
• CAS: 1308655-78-8
• 化学式: C₁₂H₁₀ClN₃O
• mdl: MFCD25819076
• 分子量: 247.684
• InChiKey: OAHJUPONZGRPJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-chloro-4-aminophenyl)-2-picolinamide 在 四(三苯基膦)钯 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 13.0h， 生成 N-(3-chloro-4-(4-trimethylstannyl-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide
  参考文献：
  名称：

  Radiosynthesis and Evaluation of an ¹⁸F-Labeled Positron Emission Tomography (PET) Radioligand for Metabotropic Glutamate Receptor Subtype 4 (mGlu₄)

  摘要：

  Four 4-phthalimide derivatives of N-(3-chlorophenyl)-2-picolinamide were synthesized as potential ligands for the PET imaging of mGlu4 in the brain. Of these compounds, N-(3-chloro-4-(4-fluoro-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide (3, KALB001) exhibited improved binding affinity (IC50 = 5.1 nM) compared with ML128 (1) and was subsequently labeled with F-18. When finally formulated in 0.1 M citrate buffer (pH 4) with 10% ethanol, the specific activity of [F-18]3 at the end of synthesis (EOS) was 233.5 +/- 177.8 GBq/mu mol (n = 4). The radiochemical yield of [F-18]3 was 16.4 +/- 4.8% (n = 4), and the purity was over 98%. In vivo imaging studies in a monkey showed that the radiotracer quickly penetrated the brain with the highest accumulation in the brain areas known to express mGlu4. Despite some unfavorable radiotracer properties like fast washout in rodent studies, [F-18]3 is the first F-18-labeled mGlu4 radioligand, which can be further modified to improve pharmacokinetics and brain penetrability for future human studies.

  DOI：

  10.1021/jm501245b
• 作为产物：
  描述：

  N,N-二boc-2-氯-4-硝基苯胺 在 盐酸 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 44.25h， 生成 N-(3-chloro-4-aminophenyl)-2-picolinamide
  参考文献：
  名称：

  Discovery, Synthesis, and Structure−Activity Relationship Development of a Series of N-(4-Acetamido)phenylpicolinamides as Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4 (mGlu₄) with CNS Exposure in Rats

  摘要：

  Herein we report the discovery, synthesis, and evaluation of a series of N-(4-acetamido)-phenylpico-linamides as positive allosteric modulators of mGlu(4). Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats.

  DOI：

  10.1021/jm101271s

文献信息

• SUBSTITUTED DIOXOPIPERIDINES AND DIOXOPYRROLIDINES AS MGLUR4 ALLOSTERIC POTENTIATORS, COMPOSITIONS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTION
  申请人：Conn P. Jeffrey

  公开号：US20110124663A1

  公开（公告）日：2011-05-26

  In one aspect, the invention relates to compounds having a general structure: wherein the variables are defined herein, which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及具有一般结构的化合物：其中变量如本文所定义，这些化合物可用作代谢型谷氨酸受体亚型4（mGluR4）的变构增强剂/正变构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物的方法，例如在治疗神经和精神障碍或其他与谷氨酸功能障碍相关的疾病状态中。本摘要旨在作为在特定领域搜索的扫描工具，并不意味着对本发明的限制。
• US8759377B2
  申请人：——

  公开号：US8759377B2

  公开（公告）日：2014-06-24
• Radiosynthesis and Evaluation of an ¹⁸F-Labeled Positron Emission Tomography (PET) Radioligand for Metabotropic Glutamate Receptor Subtype 4 (mGlu₄)
  作者：Kun-Eek Kil、Pekka Poutiainen、Zhaoda Zhang、Aijun Zhu、Ji-Kyung Choi、Kimmo Jokivarsi、Anna-Liisa Brownell

  DOI：10.1021/jm501245b

  日期：2014.11.13

  Four 4-phthalimide derivatives of N-(3-chlorophenyl)-2-picolinamide were synthesized as potential ligands for the PET imaging of mGlu4 in the brain. Of these compounds, N-(3-chloro-4-(4-fluoro-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide (3, KALB001) exhibited improved binding affinity (IC50 = 5.1 nM) compared with ML128 (1) and was subsequently labeled with F-18. When finally formulated in 0.1 M citrate buffer (pH 4) with 10% ethanol, the specific activity of [F-18]3 at the end of synthesis (EOS) was 233.5 +/- 177.8 GBq/mu mol (n = 4). The radiochemical yield of [F-18]3 was 16.4 +/- 4.8% (n = 4), and the purity was over 98%. In vivo imaging studies in a monkey showed that the radiotracer quickly penetrated the brain with the highest accumulation in the brain areas known to express mGlu4. Despite some unfavorable radiotracer properties like fast washout in rodent studies, [F-18]3 is the first F-18-labeled mGlu4 radioligand, which can be further modified to improve pharmacokinetics and brain penetrability for future human studies.
• Discovery, Synthesis, and Structure−Activity Relationship Development of a Series of <i>N</i>-(4-Acetamido)phenylpicolinamides as Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4 (mGlu₄) with CNS Exposure in Rats
  作者：Darren W. Engers、Julie R. Field、Uyen Le、Ya Zhou、Julie D. Bolinger、Rocio Zamorano、Anna L. Blobaum、Carrie K. Jones、Satyawan Jadhav、C. David Weaver、P. Jeffrey Conn、Craig W. Lindsley、Colleen M. Niswender、Corey R. Hopkins

  DOI：10.1021/jm101271s

  日期：2011.2.24

  Herein we report the discovery, synthesis, and evaluation of a series of N-(4-acetamido)-phenylpico-linamides as positive allosteric modulators of mGlu(4). Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats.