(±)-(4-fluorophenyl)(3-methylpiperazin-1-yl)methanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (±)-(4-fluorophenyl)(3-methylpiperazin-1-yl)methanone
• 英文别名: 1-(4-Fluorobenzoyl)-3-methylpiperazine；(4-fluorophenyl)-(3-methylpiperazin-1-yl)methanone
• 化学式: C₁₂H₁₅FN₂O
• 分子量: 222.262
• InChiKey: GFYPGLIUERDLAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯-4'-氟苯丁酮 、 (±)-(4-fluorophenyl)(3-methylpiperazin-1-yl)methanone 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 4-[4-(4-Fluorobenzoyl)-2-methylpiperazin-1-yl]-1-(4-fluorophenyl)butan-1-one
  参考文献：
  名称：

  7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics

  摘要：

  Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)- a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bioavailability. These variations included a series of piperazine, ethanediamine, and piperidine derivatives. The piperidine series afforded some orally potent compounds in the inhibition of apomorphine-induced climbing and hyperactivity in mice, which are regarded as behavioral models predictive of antipsychotic efficacy. Further optimization of these structures led to the highly potent 7-[3-(1-piperidinyl)propoxy]chromenones. Inhibition of stereotypies and induction of catalepsy in rats at doses substantially higher than required for inhibition of climbing suggest an atypical antipsychotic profile, which is assumed to predict a reduced induction of extrapyramidal side effects in humans.

  DOI：

  10.1021/jm950894b
• 作为产物：
  描述：

  2-甲基哌嗪 、 对氟苯甲酰氯 在 碳酸氢钠 作用下， 以 丙酮 为溶剂， 反应 1.5h， 以48%的产率得到(±)-(4-fluorophenyl)(3-methylpiperazin-1-yl)methanone
  参考文献：
  名称：

  7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics

  摘要：

  Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)- a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bioavailability. These variations included a series of piperazine, ethanediamine, and piperidine derivatives. The piperidine series afforded some orally potent compounds in the inhibition of apomorphine-induced climbing and hyperactivity in mice, which are regarded as behavioral models predictive of antipsychotic efficacy. Further optimization of these structures led to the highly potent 7-[3-(1-piperidinyl)propoxy]chromenones. Inhibition of stereotypies and induction of catalepsy in rats at doses substantially higher than required for inhibition of climbing suggest an atypical antipsychotic profile, which is assumed to predict a reduced induction of extrapyramidal side effects in humans.

  DOI：

  10.1021/jm950894b

文献信息

• Substituted 4-(1H-imidazol-1-yl)benzamides as antiarrhythmic agents
  申请人：Schering A.G.

  公开号：US04804662A1

  公开（公告）日：1989-02-14

  Novel substituted 4-[1H-imidazol-1-yl]benzamides and their use in the treatment of cardiac arrthythmias especially as Class III or combination Class I/III antiarrhythmic agents is described. Pharmaceutical formulations containing such compounds are also disclosed.

  本文介绍了一种替代品，即4-[1H-咪唑-1-基]苯甲酰胺，以及它们在治疗心律失常方面的应用，特别是作为III类或I/III类联合抗心律失常药物。还公开了含有这种化合物的制药配方。
• Substituted 4-[1H-Imidazol-1-yl] benzamides as antiarrhythmic agents
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP0290377A1

  公开（公告）日：1988-11-09

  Novel substituted 4-[1H-imidazol-1-yl]benzamides and their use in the treatment of cardiac arrhythmias especially as Class III or combination Class I/III antiarrhythmic agents is described. Pharmaceutical formulations containing such compounds are also disclosed.

  描述了新型取代的 4-[1H-咪唑-1-基]苯甲酰胺及其在治疗心律失常中的用途，特别是作为 III 类或 I/III 类抗心律失常联合药物。还公开了含有此类化合物的药物制剂。
• US4804662A
  申请人：——

  公开号：US4804662A

  公开（公告）日：1989-02-14
• Design, synthesis, and biological evaluation of novel 2-methylpiperazine derivatives as potent CCR5 antagonists
  作者：Suwen Hu、Zhilong Wang、Tingjun Hou、Xiaodong Ma、Jing Li、Tao Liu、Xin Xie、Yongzhou Hu

  DOI：10.1016/j.bmc.2014.12.052

  日期：2015.3

  Three series of novel 2-methylpiperazine derivatives were designed and synthesized using a fragment-assembly strategy. Among them, six compounds (13, 16, 18, 22, 33, and 36) showed potent activity against CCR5 comparable to that of the positive control, maraviroc, in calcium mobilization assay. Moreover, some compounds were selected and further tested for their antiviral activity in HIV-1 single cycle assay. As a result, four compounds (13, 16, 33, and 36) showed antiviral activity at the nanomolar level. Additionally, the potent four compounds showed no cytotoxicity at a concentration of 10 mu M. (C) 2015 Elsevier Ltd. All rights reserved.
• 7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics
  作者：Jordi Bolós、Santiago Gubert、Lluís Anglada、Josep M. Planas、Carme Burgarolas、Josep M. Castelló、Aurelio Sacristán、José A. Ortiz

  DOI：10.1021/jm950894b

  日期：1996.1.1

  Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)- a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bioavailability. These variations included a series of piperazine, ethanediamine, and piperidine derivatives. The piperidine series afforded some orally potent compounds in the inhibition of apomorphine-induced climbing and hyperactivity in mice, which are regarded as behavioral models predictive of antipsychotic efficacy. Further optimization of these structures led to the highly potent 7-[3-(1-piperidinyl)propoxy]chromenones. Inhibition of stereotypies and induction of catalepsy in rats at doses substantially higher than required for inhibition of climbing suggest an atypical antipsychotic profile, which is assumed to predict a reduced induction of extrapyramidal side effects in humans.