1-(2,4-dichlorophenyl)-4-cyano-5-(4-([11C]methoxy)phenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide | 942063-86-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2,4-dichlorophenyl)-4-cyano-5-(4-([11C]methoxy)phenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
• 英文别名: 11c-Omar；4-cyano-1-(2,4-dichlorophenyl)-5-(4-(111C)methoxyphenyl)-N-piperidin-1-ylpyrazole-3-carboxamide
• CAS: 942063-86-7
• 化学式: C₂₃H₂₁Cl₂N₅O₂
• 分子量: 469.347
• InChiKey: MCNQUWLLXZZZAC-BJUDXGSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  83.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl N-[2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)oxan-3-yl]carbamate 生成 1-(2,4-dichlorophenyl)-4-cyano-5-(4-([11C]methoxy)phenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Bioorganic and Medicinal Chemistry Letters. 2012, 22, 3704-3709

  摘要：

  DOI：

文献信息

• A new high-yield synthetic route to PET CB1 radioligands [11C]OMAR and its analogs
  作者：Mingzhang Gao、Min Wang、Qi-Huang Zheng

  DOI：10.1016/j.bmcl.2012.04.030

  日期：2012.6

  OMAR analogs reference standards and their corresponding desmethylated precursors were synthesized from substituted anilines either in 4 and 5 steps with 27–32% and 24–31% yield, or in 3 and 4 steps with 21–30% and 19–28% yield, respectively. [11C]OMAR and its analog radioligands were prepared from their desmethylated precursors with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined

  OMAR类似物参考标准品及其相应的去甲基化前体是由取代的苯胺分4步和5步合成的，产率为27–32％和24–31％，或分3步和4步合成的，产率为21–30％和19–28％，分别。[ 11 C] OMAR及其类似物放射性配体由具有[ 11 C] CH 3 OTf的脱甲基前体通过O- [ 11 C]甲基化制备，并通过HPLC结合固相萃取（SPE）在50-65％的放射化学中进行分离产生基于[ 11 C] CO 2的化合物，并将其衰减校正为轰击结束（EOB），在EOB处的比活为370–740 GBq /μmol。
• Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[11C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([11C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[11C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([11C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor
  作者：Hong Fan、Hayden T. Ravert、Daniel P. Holt、Robert F. Dannals、Andrew G. Horti

  DOI：10.1002/jlcr.1125

  日期：2006.10.30

  Two novel ligands for cerebral cannabinoid receptor (CB1), 1-(2,4-dichlorophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (JHU75575) have been synthesized. Both JHU75528 and JHU75575 display a combination of higher binding affinity and lower lipophilicity than those of Rimonabant (SR141716), a high affinity CB1 selective antagonist, and AM281, the only available ligand for emission tomography imaging of CB1 in human subjects. Radiolabeled [11C]JHU75528 and [11C]JHU75575 were prepared by reaction of [11C]methyl iodide with nor-methyl precursors. The average radiochemical yield, specific radioactivity, and radiochemical purity of [11C]JHU75528 were 16%, 235 GBq/µmol (6360 mCi/µmol), and 99%, respectively; those of [11C]JHU75575 were 8%, 196 GBq/µmol (5308 mCi/µmol), and 99%, respectively. Both ligands hold promise as PET radioligands for imaging CB1 receptor. Copyright © 2006 John Wiley & Sons, Ltd.

  脑大麻素受体（CB1）的两种新型配体--1-（2、合成了 1-(2,4-二氯苯基)-4-氰基-5-(4-甲氧基苯基)-N-(哌啶-1-基)-1H-吡唑-3-甲酰胺（JHU75528）和 1-(2-溴苯基)-4-氰基-5-(4-甲氧基苯基)-N-(哌啶-1-基)-1H-吡唑-3-甲酰胺（JHU75575）。与高亲和力 CB1 选择性拮抗剂利莫那班（SR141716）和唯一可用于人体 CB1 发射断层成像的配体 AM281 相比，JHU75528 和 JHU75575 都具有更高的结合亲和力和更低的亲脂性。放射性标记的[11C]JHU75528和[11C]JHU75575是通过[11C]甲基碘与非甲基前体反应制备的。[11C]JHU75528的平均放射化学收率、比放射性和放射化学纯度分别为16%、235 GBq/µmol（6360 mCi/µmol）和99%；[11C]JHU75575的平均放射化学收率、比放射性和放射化学纯度分别为8%、196 GBq/µmol（5308 mCi/µmol）和99%。这两种配体有望成为成像 CB1 受体的 PET 放射配体。Copyright © 2006 John Wiley & Sons, Ltd. All Rights Reserved.