5-(4-fluorophenyl)-2-<<4-(2-methoxyphenyl)-1-piperazinyl>methyl>pyrrole | 110319-92-1

• 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: 5-(4-fluorophenyl)-2-<<4-(2-methoxyphenyl)-1-piperazinyl>methyl>pyrrole
• 英文别名: 1-[5-(4-Fluoro-phenyl)-1H-pyrrol-2-ylmethyl]-4-(2-methoxy-phenyl)-piperazine；1-[[5-(4-fluorophenyl)-1H-pyrrol-2-yl]methyl]-4-(2-methoxyphenyl)piperazine
• CAS: 110319-92-1
• 化学式: C₂₂H₂₄FN₃O
• 分子量: 365.45
• InChiKey: VHRUYTMJYBYBCS-UHFFFAOYSA-N

物化性质

• 熔点：
  116-118.5 °C
• 沸点：
  527.5±50.0 °C(Predicted)
• 密度：
  1.206±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  31.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-甲氧苯基)哌嗪 在 溶剂黄146 作用下， 以 水 为溶剂， 反应 16.5h， 生成 5-(4-fluorophenyl)-2-<<4-(2-methoxyphenyl)-1-piperazinyl>methyl>pyrrole
  参考文献：
  名称：

  2-Phenylpyrroles as conformationally restricted benzamide analogs. A new class of potential antipsychotics. 1

  摘要：

  2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or to the 4-substituted piperazine moiety of fluanisone but is lost if the 2-phenylpyrrole is combined with the 4-substituted piperidine moiety of haloperidol. The 2-phenylpyrrole analogue 1 of sultopride is in vitro 0.25 and in vivo 3 times as potent as the parent compound. Its binding to the dopamine D-2 receptors is, in analogy to the substituted benzamides, strongly sodium-dependent. The 2-(4-fluorophenyl)pyrrole analogue 5 of fluanisone is superior in vitro as well as in vivo to the corresponding benzamide 7 and the butyrophenone fluanisone. The increase in activity is not only due to a higher affinity for the D-2 receptors but also to an enhanced oral absorption (ratio po/ip = 4.5 vs 40 for the benzamide and 60 for fluanisone). Compound 5 is further characterized by a high selectivity for the D-2 receptors, in contrast to the benzamide and butyrophenone analogues (ratio D-2/alpha 1 = 60, 2.0, and 0.3, respectively). The binding to the D-2 receptors has little dependence on sodium. The 2-phenylpyrrole 5 shares with the benzamide 7 a low potential to induce catalepsy, which is in contrast to haloperidol. So, 5-(4-fluorophenyl)-2-[[4-(2-methoxyphenyl)-1-piperazinyl]methyl]pyrrole (5) is the prototype of a new class of sodium-independent dopamine D-2 antagonists, which may be particularly useful as potential antipsychotics with a low propensity to induce acute extrapyramidal side effects.

  DOI：

  10.1021/jm00394a028

文献信息

• 2-Phenylpyrroles as conformationally restricted benzamide analogs. A new class of potential antipsychotics. 2
  作者：Ineke Van Wijngaarden、Chris G. Kruse、Jan A. M. Van der Heyden、Martin T. M. Tulp

  DOI：10.1021/jm00118a011

  日期：1988.10

  A series of 2-phenylpyrrole Mannich bases was synthesized and screened in pharmacological models for antipsychotic activity and extrapyramidal effects. Structure modifications of 5-(4-fluorophenyl)-2-[[4-(2-methoxyphenyl)-1-piperazinyl]methyl]pyrrole (1), the prototype of a new class of sodium-independent atypical dopamine D-2 antagonists, resulted in 2-[[4-(7-benzofuranyl)-1-piperazinyl]methyl]-5

  合成了一系列2-苯基吡咯曼尼希碱，并在药理模型中筛选了抗精神病活性和锥体束外作用。5-（4-氟苯基）-2-[[4-（2-甲氧基苯基）-1-哌嗪基]甲基]吡咯的结构修饰（1），是新型的钠依赖性非典型多巴胺D-2拮抗剂的原型，产生2-[[[4-（7-苯并呋喃基）-1-哌嗪基]甲基] -5-（4-氟苯基）吡咯（15），它是比母体化合物更有效和选择性的D-2拮抗剂。阿朴吗啡诱导的攀爬行为具有出色的口服活性，并且有条件的回避反应测试以及没有僵住症，使得该化合物作为潜在的抗精神病药特别有前景，且诱发急性锥体外系副作用的可能性低。
• Aryl-substituted (N-piperidinyl)-methyl- and (N-piperazinyl) methylazoles having antipsychotic properties
  申请人：DUPHAR INTERNATIONAL RESEARCH B.V

  公开号：EP0241053A1

  公开（公告）日：1987-10-14

  The invention relates to new aryl-substituted (N-piperidinyl)methyl- and (N-piperazinyl)methylazoles having interesting pharmacological, notably antipsychotic, properties. The compounds may be prepared in a manner known for the synthesis of analogous compounds and be processed to compositions according to known methods.

  本发明涉及新的芳基取代(N-哌啶基)甲基和(N-哌嗪基)甲基唑，具有有趣的药理特性，特别是抗精神病特性。 这些化合物可以按照合成类似化合物的已知方式制备，并按照已知方法加工成组合物。
• VAN, WIJNGAARDEN INEKE;KRUSE, CHRIS G.;VAN, HES ROELOF;VAN, DER HEYDEN JA+, J. MED. CHEM., 30,(1987) N 11, 2099-2104
  作者：VAN, WIJNGAARDEN INEKE、KRUSE, CHRIS G.、VAN, HES ROELOF、VAN, DER HEYDEN JA+

  DOI：——

  日期：——
• VAN, WIJNGAARDEN INEKE;KRUSE, CHRIS G.;VAN, DER HEYDEN JAN A. M.;TULP, MA+, J. MED. CHEM., 31,(1988) N 10, C. 1934-1940
  作者：VAN, WIJNGAARDEN INEKE、KRUSE, CHRIS G.、VAN, DER HEYDEN JAN A. M.、TULP, MA+

  DOI：——

  日期：——
• US4772604A
  申请人：——

  公开号：US4772604A

  公开（公告）日：1988-09-20