N-(3-chloropropyl)-4-fluoro-N-(4-fluorophenyl)benzenamine | 80119-31-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(3-chloropropyl)-4-fluoro-N-(4-fluorophenyl)benzenamine
• 英文别名: N-(3-chloropropyl)-4-fluoro-N-(4-fluorophenyl)aniline
• CAS: 80119-31-9
• 化学式: C₁₅H₁₄ClF₂N
• 分子量: 281.733
• InChiKey: SKYHUNMPIJYLDI-UHFFFAOYSA-N

物化性质

• 沸点：
  392.7±37.0 °C(Predicted)
• 密度：
  1.242±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-chloropropyl)-4-fluoro-N-(4-fluorophenyl)benzenamine 在 sodium hydride 、 potassium carbonate 、 sodium iodide 作用下， 以 various solvent(s) 为溶剂， 反应 26.0h， 生成 8-{3-[Bis-(4-fluoro-phenyl)-amino]-propyl}-3-(2-diethylamino-ethyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one; hydrochloride
  参考文献：
  名称：

  Examination of a series of 8-[3-[bis(4-fluorophenyl)amino]propyl]-1-aryl-1,3,8-triazaspiro[4.5]decan-4-ones as potential antipsychotic agents

  摘要：

  8-[3-[Bis(4-fluorophenyl)amino]propyl]-1-phenyl-1,3,8- triazaspiro[4.5]decan-4-one (3) and related compounds have been shown to have antipsychotic profiles in biochemical and behavioral pharmacological test models. The dose of 3 necessary to produce catalepsy in rats is much greater than that required for activity in behavioral tests predictive of antipsychotic efficacy, for example the suppression of high base line medial forebrain bundle self-stimulation in rats. This suggests that 3 would have a reduced propensity for neurological side effects. The effects of substitution on the 1-phenyl moiety and on the N-3 nitrogen atom of the triazaspirodecanone portion of 3 were examined. Results from this study suggest that behavioral activity is sensitive to substituents on the 1-phenyl moiety while substituents on the N-3 nitrogen are more generally tolerated. In both rats and squirrel monkeys compound 3 was found to have a similar separation between doses inhibiting Sidman avoidance activity and those causing catalepsy. However, in an extrapyramidal side effect (EPS) test model using haloperidol-sensitized cebus monkeys, 3 elicited signs of EPS at doses approximating those previously determined to be efficacious.

  DOI：

  10.1021/jm00150a011
• 作为产物：
  描述：

  4,4'-二氟二苯胺 在 硼烷 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 8.0h， 生成 N-(3-chloropropyl)-4-fluoro-N-(4-fluorophenyl)benzenamine
  参考文献：
  名称：

  1- [3-（二芳基氨基）丙基]哌啶和相关化合物，潜在的抗精神病药，具有低致肽原性特征。

  摘要：

  基于突触后多巴胺能拮抗剂药效基团的结构模型，合成了一系列1- [3-（二芳基氨基）丙基]哌啶及其相关化合物，并评估了其潜在的抗精神病活性。为了快速测定活性，首先在体外测试了目标化合物对[3H]氟哌啶醇结合的抑制作用，然后在体内进行了运动活性测试。通过抑制高基线内侧前脑束自我刺激测试模型，可以更准确地测量从初始筛选中鉴定出的化合物的行为功效。这些化合物引起锥体束外副作用的倾向通过使用大鼠僵直方法进行评估。在这些测试模型的基础上，我们表明1-（4，4-二芳基丁基）哌啶可有利地被氮原子取代。1- [3-（二芳基氨基）丙基]哌啶比相应的1-（4,4-二芳基丁基）哌啶具有较低的致敏性。有效剂量和致死剂量之间间隔最大的化合物是8- [3- [双[4-（氟代苯基）氨基]丙基] -1-苯基-1,3,8-三氮杂螺[4]。5] decan-4-one（6），1- [1- [3- [双（4-（氟代苯基）氨基]丙基]

  DOI：

  10.1021/jm50001a013

文献信息

• Analogs of penfluridol as chemotherapeutic agents with reduced central nervous system activity
  作者：Md Ashraf-Uz-Zaman、Md Sanaullah Sajib、Luca Cucullo、Constantinos M. Mikelis、Nadezhda A. German

  DOI：10.1016/j.bmcl.2018.10.036

  日期：2018.12

  as a chemotherapeutic agent. In vivo experiments have confirmed the cytotoxic activity of penfluridol in triple-negative breast cancer model, lung cancer model, and further studies have been proposed to assess its anticancer activity and viability for the treatment of glioblastomas. However, penfluridol anticancer activity was observed at a dosage significantly higher than that administered in antipsychotic

  最近的几份报告强调了使用众所周知的抗精神病药物五氟利多作为化疗药物的可行性。体内实验已经证实了五氟利多在三阴性乳腺癌模型、肺癌模型中的细胞毒活性，并且已经提出进一步的研究来评估其抗癌活性和治疗胶质母细胞瘤的可行性。然而，在剂量显着高于抗精神病药物治疗的剂量下观察到五氟利多的抗癌活性，因此引发了对接受强化药物治疗的患者可能出现中枢神经系统副作用的担忧。在这项研究中，我们与一组类似物并排评估了五氟利多的潜在 CNS 毒性。
• WISE, L. D.;PATTISON, I. C.;BUTLER, D. E.;DEWALD, H. A.;LEWIS, E. P.;LOBB+, J. MED. CHEM., 1985, 28, N 12, 1811-1817
  作者：WISE, L. D.、PATTISON, I. C.、BUTLER, D. E.、DEWALD, H. A.、LEWIS, E. P.、LOBB+

  DOI：——

  日期：——
• Examination of a series of 8-[3-[bis(4-fluorophenyl)amino]propyl]-1-aryl-1,3,8-triazaspiro[4.5]decan-4-ones as potential antipsychotic agents
  作者：Lawrence D. Wise、Ian C. Pattison、Donald E. Butler、Horace A. DeWald、Edward P. Lewis、Sandra J. Lobbestael、Haile Tecle、Linda L. Coughenour、David A. Downs、B. P. H. Poschel

  DOI：10.1021/jm00150a011

  日期：1985.12

  8-[3-[Bis(4-fluorophenyl)amino]propyl]-1-phenyl-1,3,8- triazaspiro[4.5]decan-4-one (3) and related compounds have been shown to have antipsychotic profiles in biochemical and behavioral pharmacological test models. The dose of 3 necessary to produce catalepsy in rats is much greater than that required for activity in behavioral tests predictive of antipsychotic efficacy, for example the suppression of high base line medial forebrain bundle self-stimulation in rats. This suggests that 3 would have a reduced propensity for neurological side effects. The effects of substitution on the 1-phenyl moiety and on the N-3 nitrogen atom of the triazaspirodecanone portion of 3 were examined. Results from this study suggest that behavioral activity is sensitive to substituents on the 1-phenyl moiety while substituents on the N-3 nitrogen are more generally tolerated. In both rats and squirrel monkeys compound 3 was found to have a similar separation between doses inhibiting Sidman avoidance activity and those causing catalepsy. However, in an extrapyramidal side effect (EPS) test model using haloperidol-sensitized cebus monkeys, 3 elicited signs of EPS at doses approximating those previously determined to be efficacious.
• 1-[3-(Diarylamino)propyl]piperidines and Related Compounds, Potential Antipsychotic Agents with Low Cataleptogenic Profiles
  作者：Lawrence D. Wise、Ian C. Pattison、Donald E. Butler、Horace A. DeWald、Edward P. Lewis、Sandra J. Lobbestael、Ivan C. Nordin、B. P. H. Poschel、Linda L. Coughenour

  DOI：10.1021/jm50001a013

  日期：1985.5

  antagonist pharmacophore, a series of 1-[3-(diarylamino)propyl]piperidines and related compounds was synthesized and evaluated for potential antipsychotic activity. For a rapid measure of activity, the target compounds were initially screened in vitro for inhibition of [3H]haloperidol binding and in vivo in a test of locomotor activity. Behavioral efficacy of compounds identified from the initial screens

  基于突触后多巴胺能拮抗剂药效基团的结构模型，合成了一系列1- [3-（二芳基氨基）丙基]哌啶及其相关化合物，并评估了其潜在的抗精神病活性。为了快速测定活性，首先在体外测试了目标化合物对[3H]氟哌啶醇结合的抑制作用，然后在体内进行了运动活性测试。通过抑制高基线内侧前脑束自我刺激测试模型，可以更准确地测量从初始筛选中鉴定出的化合物的行为功效。这些化合物引起锥体束外副作用的倾向通过使用大鼠僵直方法进行评估。在这些测试模型的基础上，我们表明1-（4，4-二芳基丁基）哌啶可有利地被氮原子取代。1- [3-（二芳基氨基）丙基]哌啶比相应的1-（4,4-二芳基丁基）哌啶具有较低的致敏性。有效剂量和致死剂量之间间隔最大的化合物是8- [3- [双[4-（氟代苯基）氨基]丙基] -1-苯基-1,3,8-三氮杂螺[4]。5] decan-4-one（6），1- [1- [3- [双（4-（氟代苯基）氨基]丙基]