2-(1-ethyl-2-pyrrolidinyl)-5-<5-(ethylsulfonyl)-2-methoxyphenyl>pyrrole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-(1-ethyl-2-pyrrolidinyl)-5-<5-(ethylsulfonyl)-2-methoxyphenyl>pyrrole
• 英文别名: 2-(2-methoxy-5-ethylsulfonylphenyl)-5-(N-ethyl-2-pyrrolidinyl)pyrrole；2-(1-ethylpyrrolidin-2-yl)-5-(5-ethylsulfonyl-2-methoxyphenyl)-1H-pyrrole
• 化学式: C₁₉H₂₆N₂O₃S
• 分子量: 362.493
• InChiKey: PWMDANRQWZFAPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 2-(1-ethyl-2-pyrrolidinyl)-5-<5-(ethylsulfonyl)-2-methoxyphenyl>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

• Phenyl, Pyrrolidin-2-yl substituted pyrroles having antipsychotic
  申请人：Duphar International Research B.V.

  公开号：US04791132A1

  公开（公告）日：1988-12-13

  The invention relates to a group of new phenyl, pyrrolidin-2-yl substituted 5-ring heterocyclic compounds of the formula ##STR1## wherein A is an unsaturated heterocyclic 5-ring having at least one nitrogen or oxygen atom in the ring, with the proviso that the phenyl substituent is in a meta-position with respect to the 2-pyrrolidinyl substituent. The compounds have interesting pharmacological, notably antipsychotic properties.

  本发明涉及一组新的苯基、吡咯烷-2-基取代的5元杂环化合物，其分子式为：##STR1## 其中，A是一种不饱和的5元杂环，其环中至少有一个氮或氧原子，且苯基取代基与2-吡咯烷基取代基的相对位置为间位。这些化合物具有有趣的药理学特性，尤其是抗精神病作用。
• Derivatives of phenyl, pyrrolidin-2-yl substituted 5-ring heterocycles having antipsychotic properties
  申请人：DUPHAR INTERNATIONAL RESEARCH B.V

  公开号：EP0259930A1

  公开（公告）日：1988-03-16

  The invention relates to a group of new phenyl, pyrrolidin-2-yl substituted 5-ring heterocyclic compounds of the formula wherein A is an unsaturated heterocylic 5-ring having at least one nitrogen or oxygen atom in the ring, with the proviso that the phenyl substituent is in a meta-position with respect to the 2-pyrrolidinyl substituent. The compounds have interesting pharmacological, notably antipsychotic properties.

  本发明涉及一组新的苯基、吡咯烷-2-基取代的 5 环杂环化合物，其式为 其中 A 是不饱和杂环 5-环，环中至少有一个氮原子或氧原子，但苯基取代基相对于 2-吡咯烷基取代基处于元位置。 这些化合物具有有趣的药理特性，尤其是抗精神病特性。
• Novel 2,5-disubstituted-1H-pyrroles with high affinity for the dopamine D3 receptor
  作者：David Bolton、Izzy Boyfield、Martyn C. Coldwell、Michael S. Hadley、Maureen A.M. Healy、Christopher N. Johnson、Roger E. Markwell、David J. Nash、Graham J. Riley、Geoffrey Stemp、Harry J. Wadsworth

  DOI：10.1016/0960-894x(96)00202-8

  日期：1996.6

  A series of 2,5-disubstituted-1H-pyrroles (4-18) has been prepared based on replacement of the amide of sultopride 1 by a pyrrole ring. Subsequent modification of the basic side chain gave compounds with high affinity for the dopamine D-3 receptor. In addition, 12 and 17 were shown to be D-3 antagonists with 30-fold selectivity for the D-3 receptor over the D-2 receptor. Copyright (C) 1996 Elsevier Science Ltd
• 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：——
• US4791132A
  申请人：——

  公开号：US4791132A

  公开（公告）日：1988-12-13