N-<3-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>propyl>phthalimide

• 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: N-<3-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>propyl>phthalimide
• 英文别名: 2-(3-(4-(1,2-benzothiazol-3-yl)piperazin-1-yl)propyl)-1H-isoindole-1,3(2H)-dione；2-(3-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)propyl)isoindoline-1,3-dione；2-[3-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-propyl]-isoindole-1,3-dione；2-[3-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]propyl]isoindole-1,3-dione
• 化学式: C₂₂H₂₂N₄O₂S
• 分子量: 406.508
• InChiKey: UHYQVVJUEINPTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  85
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-<3-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>propyl>phthalimide 在 水 、 甲胺 作用下， 反应 72.0h， 生成 3-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]propan-1-amine
  参考文献：
  名称：

  Novel Arylsulfonamide Derivatives with 5-HT₆/5-HT₇ Receptor Antagonism Targeting Behavioral and Psychological Symptoms of Dementia

  摘要：

  In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design to obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5-HT6/7/2A and D-2 receptors, without interacting with M-1 receptors and hERG channels. In vitro studies confirmed their antagonism of 5-HT7/2A and D-2 receptors and weak interactions with key antitargets (M1R and hERG) associated with side effects. Marked 5-HT6 receptor affinities were also observed, notably for 6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole derivatives connected by a 3-4 unit alkyl linker with mono- or bicyclic, lipophilic arylsulfonamide moieties. N-[4-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]benzothiophene-2-sulfonamide (72) was characterized in vitro on 14 targets and antitargets. It displayed dual blockade of 5-HT6 and D-2 receptors and negligible interactions at hERG and M-1 receptors. Unlike reference antipsychotics, 72 displayed marked antipsychotic and antidepressant activity in rats after oral administration, in the absence of cognitive or motor impairment. This profile is particularly attractive when targeting a fragile, elderly BPSD patient population.

  DOI：

  10.1021/jm401895u
• 作为产物：
  描述：

  N-(3-溴丙基)苯二胺 、 3-(1-哌嗪基)-1,2-苯并异噻唑 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 N-<3-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>propyl>phthalimide
  参考文献：
  名称：

  Novel Arylsulfonamide Derivatives with 5-HT₆/5-HT₇ Receptor Antagonism Targeting Behavioral and Psychological Symptoms of Dementia

  摘要：

  In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design to obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5-HT6/7/2A and D-2 receptors, without interacting with M-1 receptors and hERG channels. In vitro studies confirmed their antagonism of 5-HT7/2A and D-2 receptors and weak interactions with key antitargets (M1R and hERG) associated with side effects. Marked 5-HT6 receptor affinities were also observed, notably for 6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole derivatives connected by a 3-4 unit alkyl linker with mono- or bicyclic, lipophilic arylsulfonamide moieties. N-[4-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]benzothiophene-2-sulfonamide (72) was characterized in vitro on 14 targets and antitargets. It displayed dual blockade of 5-HT6 and D-2 receptors and negligible interactions at hERG and M-1 receptors. Unlike reference antipsychotics, 72 displayed marked antipsychotic and antidepressant activity in rats after oral administration, in the absence of cognitive or motor impairment. This profile is particularly attractive when targeting a fragile, elderly BPSD patient population.

  DOI：

  10.1021/jm401895u

文献信息

• ARYLOSULFONAMIDES FOR THE TREATMENT OF CNS DISEASES
  申请人：Kolaczkowski Marcin

  公开号：US20130172365A1

  公开（公告）日：2013-07-04

  Arylsulphonamide derivatives of formula (I) and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of disorders of the central nervous system.

  化学式（I）的芳基磺胺衍生物及其药用盐。这些化合物可能对中枢神经系统疾病的治疗和/或预防有用。
• ARYLPIPERAZINE-CONTAINING PYRROLE 3-CARBOXAMIDE DERIVATIVES FOR TREATING DEPRESSIVE DISORDERS
  申请人：Lee Jinhwa

  公开号：US20110178091A1

  公开（公告）日：2011-07-21

  The present invention relates to novel arylpiperazine-containing pyrrole 3-carboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof which is useful for preventing or treating depressive disorders. The present invention also provides a method for preparing the arylpiperazine-containing pyrrole 3-carboxamide derivatives or the pharmaceutically acceptable salt thereof, a pharmaceutical composition containing same, and a method for preventing or treating depressive disorders.

  本发明涉及一种新的芳基哌嗪含有吡咯3-羧酰胺衍生物的化合物（I），或其药学上可接受的盐，用于预防或治疗抑郁症。本发明还提供了制备芳基哌嗪含有吡咯3-羧酰胺衍生物或其药学上可接受的盐的方法，包括含有它们的药物组合物，以及预防或治疗抑郁症的方法。
• Arylpiperazine-containing pyrrole 3-carboxamide derivatives for treating depressive disorders
  申请人：Lee Jinhwa

  公开号：US08895558B2

  公开（公告）日：2014-11-25

  The present invention relates to novel arylpiperazine-containing pyrrole 3-carboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof which is useful for preventing or treating depressive disorders. The present invention also provides a method for preparing the arylpiperazine-containing pyrrole 3-carboxamide derivatives or the pharmaceutically acceptable salt thereof, a pharmaceutical composition containing same, and a method for preventing or treating depressive disorders.

  本发明涉及一种新的芳基哌嗪基吡咯-3-羧酰胺衍生物（I式）或其药学上可接受的盐，用于预防或治疗抑郁症。本发明还提供了一种制备芳基哌嗪基吡咯-3-羧酰胺衍生物或其药学上可接受的盐的方法，以及含有它的制药组合物和预防或治疗抑郁症的方法。
• [EN] ARYLPIPERAZINE-CONTAINING PYRROLE 3-CARBOXAMIDE DERIVATIVES FOR TREATING DEPRESSIVE DISORDERS<br/>[FR] DÉRIVÉS DE PYRROLE 3-CARBOXAMIDE CONTENANT DE L'ARYLPIPÉRAZINE POUR LE TRAITEMENT DE TROUBLES DÉPRESSIFS
  申请人：GREEN CROSS CORP

  公开号：WO2010038948A3

  公开（公告）日：2010-06-24
• Effect of Linking Bridge Modifications on the Antipsychotic Profile of Some Phthalimide and Isoindolinone Derivatives
  作者：Mark H. Norman、Douglas J. Minick、Greg C. Rigdon

  DOI：10.1021/jm9502201

  日期：1996.1.1

  A series of phthalimide and isoindolinone derivatives bridged to 4-(1,2-benzisothiazo1-3-yl)-1-piperazinyl was prepared. The compounds were evaluated in vitro at dopamine D-2 and serotonin 5-HT1a and 5-HT2 receptors and in vivo for their ability to antagonize the apomorphine-induced climbing response in mice. The effects of bridge length and conformation on the biological activity of these potential antipsychotic agents are discussed. A four-carbon spacer provided optimal activity within the two homologous series. Conformational investigations of the lead compound, isoindolinone 2, were conducted in an attempt to account for the superior activity observed for the butyl derivatives. On the basis of NMR and molecular modeling studies, two types of folded structures were proposed and several conformationally restrained analogues were synthesized. In general, restrictions incorporated within the linking bridge were detrimental to activity.