1-(2-fluoro-5-(trifluoromethyl)benzene)piperazine | 321601-98-3

• 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: 1-(2-fluoro-5-(trifluoromethyl)benzene)piperazine
• 英文别名: 1-(2-fluoro-5-trifluoromethylphenyl)piperazine；1-[2-fluoro-5-(trifluoromethyl)phenyl]piperazine
• CAS: 321601-98-3
• 化学式: C₁₁H₁₂F₄N₂
• mdl: MFCD11872751
• 分子量: 248.223
• InChiKey: OLVOSPKOPKMMJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-(2-bromoethyl)-8-azaspiro<4,5>decane-7,9-dione 、 1-(2-fluoro-5-(trifluoromethyl)benzene)piperazine 在 三乙胺 作用下， 反应 0.5h， 以81%的产率得到8-{2-[4-(2-fluoro-5-trifluoromethylphenyl)-1-piperazinyl]ethyl}-8-azaspiro[4.5]decane-7,9-dione
  参考文献：
  名称：

  Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α_1d Adrenergic Receptor

  摘要：

  In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the aid adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially, held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three alpha(1)-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the alpha(1d)-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BAN 7378 and 69 into the putative binding sites of the alpha(1a)-AR, alpha(1b)-AR, alpha(1d)-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2, (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding, interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for alpha(1d) adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.

  DOI：

  10.1021/jm030944+
• 作为产物：
  描述：

  2-氟-5-三氟甲基苯胺 、 二(2-氯乙基)胺盐酸盐 反应 15.0h， 以74%的产率得到1-(2-fluoro-5-(trifluoromethyl)benzene)piperazine
  参考文献：
  名称：

  一种靶向多巴胺D₃受体的诊疗药物及其应用

  摘要：

  本发明涉及一种靶向多巴胺D3受体的诊疗药物及其应用，属于化学技术领域。本发明提供了靶向多巴胺D3受体的药物[18F]5b，所述药物体外稳定性好，在PBS缓冲液和胎牛血清中孵育6h内RCP均大于98％；体内稳定性好，在颅骨内的放射性摄取低，颅骨几乎不显影，体内脱氟[18F]作用可以忽略不计；在细胞水平和动物水平均对多巴胺D3受体具有特异性结合；log P平均值为2.24(1.81‑2.49)，可以穿过血脑屏障而进脑，从而对脑内多巴胺D3受体进行示踪成像。综上，靶向多巴胺D3受体的药物[18F]5b在多巴胺D3受体相关疾病诊断、治疗和疗效监测的临床应用上极具前景。

  公开号：

  CN114409621B

文献信息

• CARBONYLATED (AZA) CYCLOHEXANES AS DOPAMINE D3 RECEPTOR LIGANDS
  申请人：Capet Marc

  公开号：US20090286801A1

  公开（公告）日：2009-11-19

  The invention relates to compounds of the general formula (I): to the process for preparing them, and to the use thereof as a therapeutic agent.

  该发明涉及通式(I)的化合物，其制备过程以及作为治疗剂的用途。
• Carbonylated (aza) cyclohexanes as dopamine D3 receptor ligands
  申请人：Capet Marc

  公开号：US08802678B2

  公开（公告）日：2014-08-12

  The invention relates to compounds of the general formula (I): to the process for preparing them, and to the use thereof as a therapeutic agent.

  该发明涉及通式(I)的化合物，其制备过程以及作为治疗剂的用途。
• WO2007/148208
  申请人：——

  公开号：——

  公开（公告）日：——
• CARBONYLATED (AZA)CYCLOHEXANES AS DOPAMINE D3 RECEPTOR LIGANDS
  申请人：BIOPROJET

  公开号：EP2038268A2

  公开（公告）日：2009-03-25
• US8802678B2
  申请人：——

  公开号：US8802678B2

  公开（公告）日：2014-08-12