4-chloro-1-(4-fluorophenyl)-2-methylenebutan-1-one | 1366349-27-0

• 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-chloro-1-(4-fluorophenyl)-2-methylenebutan-1-one
• 英文别名: 4-Chloro-1-(4-fluorophenyl)-2-methylidenebutan-1-one；4-chloro-1-(4-fluorophenyl)-2-methylidenebutan-1-one
• CAS: 1366349-27-0
• 化学式: C₁₁H₁₀ClFO
• 分子量: 212.651
• InChiKey: ZTJYCNNPIVCFFD-UHFFFAOYSA-N

物化性质

• 沸点：
  306.1±42.0 °C(predicted)
• 密度：
  1.175±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-1-(4-fluorophenyl)-2-methylenebutan-1-one 在 硫酸 、 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 49.0h， 生成 2'-(2-chloroethyl)-5'-fluoro-2',3'-dihydrospiro[[1,3]dioxolane-2,1'-indene]
  参考文献：
  名称：

  Identification of a new selective dopamine D4 receptor ligand

  摘要：

  The dopamine D-4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D-4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective and increased affinity to the DAD(4) receptor subtype, in comparison to its piperidine analog. This led to further exploration of the piperazine moiety to identify new agents that are selective at the D-4 receptor. Compound 27 (KiD4 = 0.84 nM) was the most potent of the compounds tested. However, it only had moderate selectivity for the D-4 receptor. Compound 28 (KiD4 = 3.9 nM) while not as potent, was more discriminatory for the D-4 receptor subtype. In fact, compound 28 has little or no binding affinity to any of the other four DA receptor subtypes. In addition, of the 23 CNS receptors evaluated, only two, 5HT(1A)R and 5HT(2B)R, have binding affinity constants better than 100 nM (K-i < 100 nM). Compound 28 is a potentially useful D-4-selective ligand for probing disease treatments involving the D-4 receptor, such as assisting smoking cessation, reversing cognitive deficits in schizophrenia and treating erectile dysfunction. Thus, further optimization, functional characterization and evaluation in animal models may be warranted. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.04.026
• 作为产物：
  描述：

  乌洛托品 、 4-氯-4'-氟苯丁酮 在 乙酸酐 作用下， 反应 16.0h， 以26.4%的产率得到4-chloro-1-(4-fluorophenyl)-2-methylenebutan-1-one
  参考文献：
  名称：

  Identification of a new selective dopamine D4 receptor ligand

  摘要：

  The dopamine D-4 receptor has been shown to play key roles in certain CNS pathologies including addiction to cigarette smoking. Thus, selective D-4 ligands may be useful in treating some of these conditions. Previous studies in our laboratory have indicated that the piperazine analog of haloperidol exhibits selective and increased affinity to the DAD(4) receptor subtype, in comparison to its piperidine analog. This led to further exploration of the piperazine moiety to identify new agents that are selective at the D-4 receptor. Compound 27 (KiD4 = 0.84 nM) was the most potent of the compounds tested. However, it only had moderate selectivity for the D-4 receptor. Compound 28 (KiD4 = 3.9 nM) while not as potent, was more discriminatory for the D-4 receptor subtype. In fact, compound 28 has little or no binding affinity to any of the other four DA receptor subtypes. In addition, of the 23 CNS receptors evaluated, only two, 5HT(1A)R and 5HT(2B)R, have binding affinity constants better than 100 nM (K-i < 100 nM). Compound 28 is a potentially useful D-4-selective ligand for probing disease treatments involving the D-4 receptor, such as assisting smoking cessation, reversing cognitive deficits in schizophrenia and treating erectile dysfunction. Thus, further optimization, functional characterization and evaluation in animal models may be warranted. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.04.026

文献信息

• Structure–activity relationship studies of SYA 013, a homopiperazine analog of haloperidol
  作者：Kwakye Peprah、Xue Y. Zhu、Suresh V.K. Eyunni、Jagan R. Etukala、Vincent Setola、Bryan L. Roth、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2012.01.022

  日期：2012.3

  Structure-activity relationship studies on 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl) butan-1-one (SYA 013), a homopiperazine analog of haloperidol has resulted in an understanding of the effect of structural modifications on binding affinity at dopamine and serotonin receptor subtypes. Further exploration, using bioisosteric replacement strategies has led to the identification of several new agents including compounds 7, 8, 11 and 12 which satisfy the initial criteria for further exploration as new antipsychotic agents. In addition, compound 18, a D-3 selective tropanol, has been identified as having the potential for further optimization into a useful drug which may combat neuropsychiatric diseases. Published by Elsevier Ltd.