2-{4-[4-(7-hydroxynaphthalen-1-yl)piperazin-1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione | 874471-23-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-{4-[4-(7-hydroxynaphthalen-1-yl)piperazin-1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione
• 英文别名: 2-(4-(4-(7-hydroxynaphthalen-1-yl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione；desmethyl-MPT；2-[4-[4-(7-Hydroxynaphthalen-1-yl)piperazin-1-yl]butyl]-4-methyl-1,2,4-triazine-3,5-dione
• CAS: 874471-23-5
• 化学式: C₂₂H₂₇N₅O₃
• 分子量: 409.488
• InChiKey: DSJDREDLRIFSQA-UHFFFAOYSA-N

物化性质

• 熔点：
  205 °C (decomp)
• 沸点：
  604.6±65.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-{4-[4-(7-hydroxynaphthalen-1-yl)piperazin-1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione 、 1-溴-2-氟乙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以70%的产率得到FEMPT
  参考文献：
  名称：

  Microfluidic radiosynthesis of [¹⁸F]FEMPT, a high affinity PET radiotracer for imaging serotonin receptors

  摘要：

  连续流微流控技术在过去十年中在放射化学中的应用有所增加，特别是用于氟-18标记放射性示踪剂的临床前和临床生产。微流控技术的主要优点是缩短反应时间、降低试剂消耗，这通常会导致增加放射化学产率和快速优化18F标记的反应参数。本文报道了通过微流控放射化学的两步法合成高亲和力的5-羟色胺1A受体部分激动剂[18F]FEMPT(pKi = 9.79; Ki = 0.16 nM)。[18F]FEMPT的孤立放射化学收率约为7%，放射化学和化学纯度均大于98%。最终产品的摩尔活性确定为大于148 GBq/µmol(大于4 Ci/µmol)。

  DOI：

  10.3762/bjoc.13.285
• 作为产物：
  描述：

  1-氨基-7-萘酚 在 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 24.5h， 生成 2-{4-[4-(7-hydroxynaphthalen-1-yl)piperazin-1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione
  参考文献：
  名称：

  Synthesis and evaluation of arylpiperazines derivatives of 3,5-dioxo-(2 H ,4 H )-1,2,4-triazine as 5-HT 1A R ligands

  摘要：

  5-HT1AR agonist or partial agonists are established drug candidates for psychiatric and neurological disorders. We have reported the synthesis and evaluation of a series of high affinity 5-HT1AR partial agonist PET imaging agents with greater selectivity over α-1AR. The characteristic of these molecules are 3,5-dioxo-(2H,4H)-1,2,4-triazine skeleton tethered to an arylpiperazine unit through an alkyl side chain. The most potent 5-HT1AR agonistic properties were found to be associated with the molecules bearing C-4 alkyl group as the linker. Therefore development of 3,5-dioxo-(2H,4H)-1,2,4-triazine bearing arylpiperazine derivatives may provide high affinity selective 5-HT1AR ligands. Herein we describe the synthesis and evaluation of the binding properties of a series of arylpiperazine analogues of 3,5-dioxo-(2H,4H)-1,2,4-triazine.

  DOI：

  10.1016/j.bmcl.2014.07.048

文献信息

• WO2006/83424
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and in Vivo Validation of [<i>O</i>-Methyl-¹¹C]2-{4-[4-(7-methoxynaphthalen-1-yl)piperazin- 1-yl]butyl}-4-methyl-2<i>H</i>-[1,2,4]triazine-3,5-dione:  A Novel 5-HT_1A Receptor Agonist Positron Emission Tomography Ligand
  作者：J. S. Dileep Kumar、Vattoly J. Majo、Shu-Chi Hsiung、Matthew S. Millak、Kuo-Peing Liu、Hadassah Tamir、Jaya Prabhakaran、Norman R. Simpson、Ronald L. Van Heertum、J. John Mann、Ramin V. Parsey

  DOI：10.1021/jm050725j

  日期：2006.1.1

  Antagonist 5-HT1A PET ligands are available, but an agonist ligand would give more information about signal transduction capacity. Synthesis and in vivo evaluation of [O-methyl-C-11]2-4-[4-(7-methoxynaphthalen-1-yl)piperazin-1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione (10), a potential high affinity (K-i = 1.36 nM) 5-HT1A agonist PET tracer is described. Piperazine 10 is a 5-HT1A agonist with an EC50 comparable to serotonin, based on cAMP formation and GTP(gamma)S binding assays. Radiosynthesis of [C-11]10 has been achieved by reacting 2-4-[4-(7-hydroxynaphthalen-1-yl)piperazin-1-yl]butyl}-4-methyl-2H-[1,2,4]triazitle-3,5-dione (9) and [C-11]CH3OTf in 25 +/- 5% (n = 15) yield at the end of synthesis (EOS). The chemical and radiochemical purities of [C-11]10 were > 99% with a specific activity 1500 +/- 300 Ci/mmol (n = 15). PET studies in anesthetized baboon demonstrate [C-11]10 specific binding, in brain regions rich in 5-HTIA receptors. Binding of [C-11]10 was blocked by WAY 100635 and 8-OH-DPAT. The regional brain volumes of distribution (V-T) of [C-11]10 in baboon correlate with [C-11]WAY100635 V-T in baboons. These data provide evidence that [C-11]10 is the first promising agonist PET tracer for the 5-HTIA receptors.
• Radiolabeled compounds and uses thereof
  申请人：Mann Joseph John

  公开号：US20080138283A1

  公开（公告）日：2008-06-12

  The present invention relates to Radiolabeled Compounds and methods of use thereof for treating or preventing a psychiatric disorder in a subject, for stabilizing the mood of a subject having a mood disorder, or as imaging agents for a serotonin receptor. Compositions comprising an imaging-effective amount of a Radiolabeled Compound are also disclosed.
• US8168786B2
  申请人：——

  公开号：US8168786B2

  公开（公告）日：2012-05-01
• [EN] RADIOLABELED COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS RADIOMARQUÉS ET LEURS UTILISATIONS
  申请人：UNIV COLUMBIA

  公开号：WO2009006227A1

  公开（公告）日：2009-01-08

  The present invention relates to Radiolabeled Compounds and methods of use thereof for treating or preventing a psychiatric disorder in a subject, for stabilizing the mood of a subject having a mood disorder, or as an imaging agents for a serotonin receptor. Compositions comprising an imaging-effective amount of a Radiolabeled Compound are also disclosed.