N-(3-chloro-4-(4-methyl-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide | 1218926-22-7

• 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-(4-methyl-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide
• 英文别名: N-[3-chloro-4-(4-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]pyridine-2-carboxamide；N-[3-chloro-4-(4-methyl-1,3-dioxoisoindol-2-yl)phenyl]pyridine-2-carboxamide
• CAS: 1218926-22-7
• 化学式: C₂₁H₁₄ClN₃O₃
• 分子量: 391.813
• InChiKey: ANBBLLOZDHXSOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  79.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-chloro-4-(4-methyl-1,3-dioxoisoindolin-2-yl)phenyl)-2-picolinamide 在 N-碘代丁二酰亚胺 、 三氟甲磺酸 作用下， 生成 N-[5-chloro-2-iodo-4-(5-iodo-4-methyl-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]pyridine-2-carboxamide
  参考文献：
  名称：

  [EN] PHTHALIMIDE DERIVATIVE METABOTROPIC GLUTAMATE R4 LIGANDS
  [FR] LIGANDS DU GLUTAMATE MÉTABOTROPIQUE R4 DÉRIVÉ DE PHTALAMIDE

  摘要：

  本文披露了一般式（I）的mGluR4阳性变构调节剂配体以及放射标记衍生物，它们被用作治疗中枢神经系统疾病的治疗剂，这些疾病受mGluR4调节，并且作为哺乳动物中mGluR4的标记和诊断成像的配体。

  公开号：

  WO2010033349A1
• 作为产物：
  描述：

  2-吡啶甲酰氯 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 20.0~100.0 ℃ 、303.99 kPa 条件下， 反应 25.0h， 生成 N-(3-chloro-4-(4-methyl-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

文献信息

• PHTHALIMIDE DERIVATIVE METABOTROPIC GLUTAMATE R4 LIGANDS
  申请人：McCauley John A.

  公开号：US20110318266A1

  公开（公告）日：2011-12-29

  Disclosed are mGluR4 positive allosteric modulator ligands of general formula (I) and radiolabeled derivates, their use as therapeutic agents for the treatment of central nervous system disorders modulated by mGluR4 and as ligands for the labeling and diagnostic imaging of mGluR4 in mammals.

  本发明揭示了通式（I）的mGluR4阳性变构调节剂配体和放射性标记衍生物，它们可作为治疗中枢神经系统疾病的治疗剂，这些疾病受mGluR4调节，同时也可作为哺乳动物体内mGluR4的标记和诊断成像的配体。
• MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 4
  申请人：The General Hospital Corporation

  公开号：US20220118117A1

  公开（公告）日：2022-04-21

  The present application provides picolinamide compounds that can be used as allosteric positron emission tomography (“PET”) imaging probes. Methods of using these compounds for treating a neurodegenerative disease are also provided.
• 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.
• [EN] PHTHALIMIDE DERIVATIVE METABOTROPIC GLUTAMATE R4 LIGANDS<br/>[FR] LIGANDS DU GLUTAMATE MÉTABOTROPIQUE R4 DÉRIVÉ DE PHTALAMIDE
  申请人：MERCK & CO INC

  公开号：WO2010033349A1

  公开（公告）日：2010-03-25

  Disclosed are mGluR4 positive allosteric modulator ligands of general formula (I) and radiolabeled derivates, their use as therapeutic agents for the treatment of central nervous system disorders modulated by mGluR4 and as ligands for the labeling and diagnostic imaging of mGluR4 in mammals.

  本文披露了一般式（I）的mGluR4阳性变构调节剂配体以及放射标记衍生物，它们被用作治疗中枢神经系统疾病的治疗剂，这些疾病受mGluR4调节，并且作为哺乳动物中mGluR4的标记和诊断成像的配体。