LY2795050(S型) | 1346133-08-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: LY2795050(S型)
• 中文别名: LY27955
• 英文名称: LY2795050
• 英文别名: (S)-3-chloro-4-(4-((2-(pyridin-3-yl)pyrrolidin-1-yl)methyl)phenoxy)benzamide；Benzamide, 3-chloro-4-(4-(((2S)-2-(3-pyridinyl)-1-pyrrolidinyl)methyl)phenoxy)-benzamide, 3-chloro-4-(4-(((2S)-2-(3-pyridinyl)-1-pyrrolidinyl)methyl)phenoxy)-；3-chloro-4-[4-[[(2S)-2-pyridin-3-ylpyrrolidin-1-yl]methyl]phenoxy]benzamide
• CAS: 1346133-08-1
• 化学式: C₂₃H₂₂ClN₃O₂
• 分子量: 407.9
• InChiKey: LOOCZNLSXJHWTG-NRFANRHFSA-N

物化性质

• 沸点：
  532.4±50.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：50 mg/mL（122.58 mM；需要超声波）

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性 LY2795050 是一种高活性的 κ-阿片受体（KOR）拮抗剂，其 IC50 值为 0.72 nM。

反应信息

• 作为产物：
  描述：

  3-(吡咯烷-2-基)吡啶 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 甲醇 、 二甲基十二/十四烷基叔胺 、 1,2-二氯乙烷 为溶剂， 生成 LY2795050(S型)
  参考文献：
  名称：

  Discovery of Aminobenzyloxyarylamides as κ Opioid Receptor Selective Antagonists: Application to Preclinical Development of a κ Opioid Receptor Antagonist Receptor Occupancy Tracer

  摘要：

  Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for K opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyppyrrolidin-1-yl)methyl)phenoxy)benzamide (25) had a K-i = 0.565 nM for kappa opioid receptor binding while having a K-i = 35.8 nM for mu opioid receptors and a K-i = 211 nM for delta opioid receptor binding. Compound 25 was also a potent antagonist of K opioid receptors when tested in vitro using a [S-35]-guanosine 5'O-[3-thiotriphosphate] ([S-35]GTP-gamma-S) functional assay in CHO cells expressing cloned human opioid receptors. Compounds were also evaluated for potential use as receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl(pyrrolidin-1-yl)methyl)phenoxy)benzamide (18) was found to have favorable properties for a tracer for receptor occupancy, including good specific versus nonspecific binding and good brain uptake.

  DOI：

  10.1021/jm200789r

文献信息

• Radiosynthesis of [¹¹C]LY2795050 for Preclinical and Clinical PET Imaging Using Cu(II)-Mediated Cyanation
  作者：Lingyun Yang、Allen F. Brooks、Katarina J. Makaravage、Huibin Zhang、Melanie S. Sanford、Peter J. H. Scott、Xia Shao

  DOI：10.1021/acsmedchemlett.8b00460

  日期：2018.12.13

  11C-cyanation reactions have enabled the synthesis of PET radiotracers from a range of readily available precursors and avoid the need to use more toxic Pd catalysts. In this work we adapt our recently developed 11C-cyanation of arylpinacolboronate (BPin) esters for the cGMP synthesis of [11C]LY2795050, a selective antagonist radiotracer for the kappa opioid receptor (KOR). [11C]LY2795050 was synthesized in 6

  铜介导的11C氰化反应使人们能够从一系列容易获得的前体中合成PET放射性示踪剂，并且避免了使用毒性更大的Pd催化剂的需求。在这项工作中，我们将我们最近开发的芳基频哪醇硼酸酯（BPin）酯的11C氰化用于[11C] LY2795050（一种κ阿片受体（KOR）的选择性拮抗剂放射性示踪剂）的cGMP合成。使用自动合成模块以6±1％的未校正放射化学产率（基于[11C] HCN，n = 3）合成[11C] LY2795050。质量控制测试证实了该剂量适用于临床前和临床PET成像（放射化学纯度> 99％；比活> 900 mCi /μmol；残留Cu <0.1μg/ mL）。PET成像是在啮齿动物和非人类灵长类动物中进行的，表现出对[11C] LY2795050的良好大脑摄取以及预期的KOR分布。[11C]芬太尼（选择性μ阿片受体（MOR）放射性示踪剂）的类似成像显示了灵长类动物大脑中MOR和KOR分布的预期区域差异。
• Discovery of Aminobenzyloxyarylamides as κ Opioid Receptor Selective Antagonists: Application to Preclinical Development of a κ Opioid Receptor Antagonist Receptor Occupancy Tracer
  作者：Charles H. Mitch、Steven J. Quimby、Nuria Diaz、Concepcion Pedregal、Marta G. de la Torre、Alma Jimenez、Qing Shi、Emily J. Canada、Steven D. Kahl、Michael A. Statnick、David L. McKinzie、Dana R. Benesh、Karen S. Rash、Vanessa N. Barth

  DOI：10.1021/jm200789r

  日期：2011.12.8

  Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for K opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyppyrrolidin-1-yl)methyl)phenoxy)benzamide (25) had a K-i = 0.565 nM for kappa opioid receptor binding while having a K-i = 35.8 nM for mu opioid receptors and a K-i = 211 nM for delta opioid receptor binding. Compound 25 was also a potent antagonist of K opioid receptors when tested in vitro using a [S-35]-guanosine 5'O-[3-thiotriphosphate] ([S-35]GTP-gamma-S) functional assay in CHO cells expressing cloned human opioid receptors. Compounds were also evaluated for potential use as receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl(pyrrolidin-1-yl)methyl)phenoxy)benzamide (18) was found to have favorable properties for a tracer for receptor occupancy, including good specific versus nonspecific binding and good brain uptake.