N-(3-(difluoromethoxy)phenyl)-2-picolinamide hydrochloride salt | 1161205-32-8

• 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-(difluoromethoxy)phenyl)-2-picolinamide hydrochloride salt
• 英文别名: N-[3-(difluoromethoxy)phenyl]pyridine-2-carboxamide;hydrochloride
• CAS: 1161205-32-8
• 化学式: C₁₃H₁₀F₂N₂O₂*ClH
• 分子量: 300.692
• InChiKey: XEXMTALPIOIZLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.36
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  51.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(3-(difluoromethoxy)phenyl)-2-picolinamide 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以79%的产率得到N-(3-(difluoromethoxy)phenyl)-2-picolinamide hydrochloride salt
  参考文献：
  名称：

  Radiosynthesis of N-(4-chloro-3-[11C]methoxyphenyl)-2-picolinamide ([11C]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4 (mGlu4)

  摘要：

  N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu(4) positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu(4) PAM to show efficacy in a preclinical Parkinson disease model upon systemic dosing. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers a possibility to investigate mGlu(4) expression in vivo under physiologic and pathological conditions. We synthesized a carbon-11 labeled ML128 ([C-11]3) as a PET radiotracer for mGlu(4), and characterized its biological properties in Sprague Dawley rats. [C-11]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [C-11]CH3I. Total synthesis time was 38 +/- 2.2 min (n = 7) from the end of bombardment to the formulation. The radioligand [C-11] 3 was obtained in 27.7 +/- 5.3% (n = 5) decay corrected radiochemical yield based on the radioactivity of [C-11]CO2. The radiochemical purity of [C-11]3 was >99%. Specific activity was 188.7 +/- 88.8 GBq/mol (n = 4) at the end of synthesis (EOS).PET images were conducted in 20 normal male Sprague Dawley rats including 11 control studies, 6 studies blocking with an mGlu(4) modulator (4) to investigate specificity and 3 studies blocking with an mGlu(5) modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [C-11]3 (peak activity between 1-3 min) in several brain areas including striatum, thalamus, hippocampus, cerebellum, and olfactory bulb following with fast washout. Blocking studies with the mGlu(4) modulator 4 showed 22-28% decrease of [C-11]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu(5). Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu(4), in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.046

文献信息

• Radiosynthesis of N-(4-chloro-3-[11C]methoxyphenyl)-2-picolinamide ([11C]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4 (mGlu4)
  作者：Kun-Eek Kil、Zhaoda Zhang、Kimmo Jokivarsi、Chunyu Gong、Ji-Kyung Choi、Sreekanth Kura、Anna-Liisa Brownell

  DOI：10.1016/j.bmc.2013.07.046

  日期：2013.10

  N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu(4) positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu(4) PAM to show efficacy in a preclinical Parkinson disease model upon systemic dosing. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers a possibility to investigate mGlu(4) expression in vivo under physiologic and pathological conditions. We synthesized a carbon-11 labeled ML128 ([C-11]3) as a PET radiotracer for mGlu(4), and characterized its biological properties in Sprague Dawley rats. [C-11]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [C-11]CH3I. Total synthesis time was 38 +/- 2.2 min (n = 7) from the end of bombardment to the formulation. The radioligand [C-11] 3 was obtained in 27.7 +/- 5.3% (n = 5) decay corrected radiochemical yield based on the radioactivity of [C-11]CO2. The radiochemical purity of [C-11]3 was >99%. Specific activity was 188.7 +/- 88.8 GBq/mol (n = 4) at the end of synthesis (EOS).PET images were conducted in 20 normal male Sprague Dawley rats including 11 control studies, 6 studies blocking with an mGlu(4) modulator (4) to investigate specificity and 3 studies blocking with an mGlu(5) modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [C-11]3 (peak activity between 1-3 min) in several brain areas including striatum, thalamus, hippocampus, cerebellum, and olfactory bulb following with fast washout. Blocking studies with the mGlu(4) modulator 4 showed 22-28% decrease of [C-11]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu(5). Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu(4), in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain. (C) 2013 Elsevier Ltd. All rights reserved.