5-溴-N-(2-(二乙基氨基)乙基)-2-吡啶甲酰胺 | 1285446-04-9

• 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
• 中文名称: 5-溴-N-(2-(二乙基氨基)乙基)-2-吡啶甲酰胺
• 英文名称: 5-bromo-N-(2-(diethylamino)ethyl)picolinamide
• 英文别名: 5-bromo-N-[2-(diethylamino)ethyl]pyridine-2-carboxamide
• CAS: 1285446-04-9
• 化学式: C₁₂H₁₈BrN₃O
• 分子量: 300.198
• InChiKey: BSMXWXBEJYOUAH-UHFFFAOYSA-N

物化性质

• 沸点：
  412.5±40.0 °C(Predicted)
• 密度：
  1.311±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：125 mg/mL（416.40 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8°C

制备方法与用途

生物活性

Melanin probe-2（化合物5）是一种无放射性的溴吡啶甲酰胺前体。它可用于合成带有18F标记的吡啶酰胺PET探针（HY-136404）。

反应信息

• 作为反应物：
  描述：

  5-溴-N-(2-(二乙基氨基)乙基)-2-吡啶甲酰胺 在 bis-triphenylphosphine-palladium(II) chloride 、 N-溴代丁二酰亚胺(NBS) 、 三(2-呋喃基)膦 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.0h， 生成 N-(2-(diethylamino)ethyl)-5-(5-(6-oxo-7-propyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-3-yl)thiazol-2-yl)picolinamide
  参考文献：
  名称：

  使用结构导向设计发现吡唑并吡啶酮作为一类新型的Gyrase B抑制剂

  摘要：

  DNA促旋酶B的ATPase亚基是一个有吸引力的抗菌靶标，这是由于细菌之间的高度保守性及其在DNA复制中的重要作用。通过使用结构指导设计优化片段筛选命中支架，发现了一类新型的吡唑并吡啶酮抑制剂。这些抑制剂显示出有效的革兰氏阳性抗菌活性，并且对临床上重要的病原体的抵抗力较低。

  DOI：

  10.1021/acsmedchemlett.5b00368
• 作为产物：
  描述：

  5-溴-2-吡啶羧酸 、 N,N-二乙基乙二胺 在 O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以90%的产率得到5-溴-N-(2-(二乙基氨基)乙基)-2-吡啶甲酰胺
  参考文献：
  名称：

  Development of ¹⁸F-Labeled Picolinamide Probes for PET Imaging of Malignant Melanoma

  摘要：

  Melanoma is an aggressive skin cancer with worldwide increasing incidence. Development of positron emission tomography (PET) probes for early detection of melanoma is critical for improving the survival rate of melanoma patients. In this research, F-18-picolinamide-based PET probes were prepared by direct radiofluorination of the bromopicolinamide precursors using no-carrier-added F-18-fluoride. The resulting probes, F-18-1, F-18-2 and F-18-3, were then evaluated in vivo by small animal PET imaging and biodistribution studies in C57BL/6 mice bearing B16F10 murine melanoma tumors. Noninvasive small animal PET studies demonstrated excellent tumor imaging contrasts for all probes, while F-18-2 showed higher tumor to muscle ratios than F-18-1 and F-18-3. Furthermore, F-18-2 demonstrated good in vivo stability as evidenced by the low bone uptake in biodistribution studies. Collectively, these findings suggest F-18-2 as a highly promising PET probe for translation into clinical detection of melanoma.

  DOI：

  10.1021/jm301740k

文献信息

• 靶向黑色素瘤的显像剂及其制备方法与应用
  申请人：华中科技大学同济医学院附属协和医院

  公开号：CN109721533A

  公开（公告）日：2019-05-07

  本申请属于放射性标记化合物领域，具体涉及到一种靶向黑色素瘤的显像剂及其制备与应用。本发明的式I化合物可作为显像剂，特别是靶向黑色素瘤的显像剂。所述化合物在体内/外特异性靶向黑色素瘤细胞，对肿瘤部位亲和力高，且具有显像剂滞留明显和理想的药代动力学特征。此外，本发明的式I化合物在靶向黑色素瘤细胞的过程中，具有代谢速度快，特别是肝脏和肾脏清除速度较快的优点，可以作为一种无创的分子探针用于黑色素瘤早期诊断及分期。最后，本发明式I化合物中的131I发射的β射线可杀死肿瘤细胞用于抑制或治疗肿瘤，特别是黑色素瘤细胞，达到诊疗一体化效果，
• Synthesis and Preclinical Evaluation of ¹⁸F-PEG₃-FPN for the Detection of Metastatic Pigmented Melanoma
  作者：Xiaodong Xu、Lujie Yuan、Lianglan Yin、Yaqun Jiang、Yongkang Gai、Qingyao Liu、Yichun Wang、Yongxue Zhang、Xiaoli Lan

  DOI：10.1021/acs.molpharmaceut.7b00607

  日期：2017.11.6

  Although F-18-5-fluoro-N-(2-[diethylamino]-ethyl)picolinamide (F-18-5-FPN) is considered a promising radiopharmaceutical for PET imaging of melanoma, it accumulates at high concentrations in the liver. The aim in this research was to optimize the structure of F-18-5-FPN with triethylene glycol to reduce liver uptake as well as improve pharmacokinetics, and to evaluate its performance in detection of melanoma liver and lung metastases. F-18-PEG(3)-FPN was successfully prepared with a high radiolabeling yield (44.68% +/- 5.99%) and radiochemical purity (> 99%). The uptake of F-18-PEG3-FPN by pigmented B16F10 melanoma cells was significantly higher than that by amelanotic melanoma A375 cells. The binding to B16F10 cells could be blocked by excess F-19-PEG(3)-FPN. On small animal PET images, B16F10 tumors, but not A375 tumors, were clearly delineated after F-18-PEG(3)-FPN injection. More importantly, F-18-PEG(3)-FPN uptake by liver (2.27 +/- 0.45 and 1.74 +/- 0.35% ID/g, at 1 and 2 h) was significantly lower than that of F-18-5-FPN, and the lesions in lung and liver could be clearly detected by F-18-PEG3-FPN PET imaging in mouse models of pulmonary or hepatic metastases. Overall, we successfully synthesized F-18-PEG(3)-FPN, which has higher labeling efficacy and better in vivo pharmacokinetics along with lower liver uptake compared to F-18-5-FPN. This suggests F-18-PEG(3)-FPN as a candidate for pigmented melanoma liver and lung metastasis detection.
• METHODS OF PARKINSONS DISEASE DIAGNOSIS AND MONITORING TREATMENT
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20150023877A1

  公开（公告）日：2015-01-22

  Embodiments of the present disclosure provide for methods of using labeled probes, methods of diagnosing Parkinson's disease and related biological events, methods of using labeled probes for monitoring and/or assessing Parkinson's disease treatment, methods of using labeled probes for diagnosing, monitoring, and/or assessing diseases with aberrant melanin-expression, and the like.
• Discovery of Pyrazolopyridones as a Novel Class of Gyrase B Inhibitors Using Structure Guided Design
  作者：Jason B. Cross、Jing Zhang、Qingyi Yang、Michael F. Mesleh、Jan Antoinette C. Romero、Bin Wang、Doug Bevan、Katherine M. Poutsiaka、Felix Epie、Terence Moy、Anu Daniel、Joseph Shotwell、Brian Chamberlain、Nicole Carter、Ole Andersen、John Barker、M. Dominic Ryan、Chester A. Metcalf、Jared Silverman、Kien Nguyen、Blaise Lippa、Roland E. Dolle

  DOI：10.1021/acsmedchemlett.5b00368

  日期：2016.4.14

  attractive antibacterial target due to high conservation across bacteria and the essential role it plays in DNA replication. A novel class of pyrazolopyridone inhibitors was discovered by optimizing a fragment screening hit scaffold using structure guided design. These inhibitors show potent Gram-positive antibacterial activity and low resistance incidence against clinically important pathogens.

  DNA促旋酶B的ATPase亚基是一个有吸引力的抗菌靶标，这是由于细菌之间的高度保守性及其在DNA复制中的重要作用。通过使用结构指导设计优化片段筛选命中支架，发现了一类新型的吡唑并吡啶酮抑制剂。这些抑制剂显示出有效的革兰氏阳性抗菌活性，并且对临床上重要的病原体的抵抗力较低。
• Development of ¹⁸F-Labeled Picolinamide Probes for PET Imaging of Malignant Melanoma
  作者：Hongguang Liu、Shuanglong Liu、Zheng Miao、Zixin Deng、Baozhong Shen、Xuechuan Hong、Zhen Cheng

  DOI：10.1021/jm301740k

  日期：2013.2.14

  Melanoma is an aggressive skin cancer with worldwide increasing incidence. Development of positron emission tomography (PET) probes for early detection of melanoma is critical for improving the survival rate of melanoma patients. In this research, F-18-picolinamide-based PET probes were prepared by direct radiofluorination of the bromopicolinamide precursors using no-carrier-added F-18-fluoride. The resulting probes, F-18-1, F-18-2 and F-18-3, were then evaluated in vivo by small animal PET imaging and biodistribution studies in C57BL/6 mice bearing B16F10 murine melanoma tumors. Noninvasive small animal PET studies demonstrated excellent tumor imaging contrasts for all probes, while F-18-2 showed higher tumor to muscle ratios than F-18-1 and F-18-3. Furthermore, F-18-2 demonstrated good in vivo stability as evidenced by the low bone uptake in biodistribution studies. Collectively, these findings suggest F-18-2 as a highly promising PET probe for translation into clinical detection of melanoma.