2-{3-[4-(4-fluorophenyl)piperazin-1-yl]propyl}-1H-isoindole-1,3(2H)-dione

• 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: 2-{3-[4-(4-fluorophenyl)piperazin-1-yl]propyl}-1H-isoindole-1,3(2H)-dione
• 英文别名: 2-(3-(4-(4-fluorophenyl)piperazin-1-yl)propyl)isoindoline-1,3-dione；2-[3-[4-(4-Fluorophenyl)piperazin-1-yl]propyl]isoindole-1,3-dione
• 化学式: C₂₁H₂₂FN₃O₂
• 分子量: 367.423
• InChiKey: VLAYACSGEAMPDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-{3-[4-(4-fluorophenyl)piperazin-1-yl]propyl}-1H-isoindole-1,3(2H)-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以73%的产率得到3-[4-(4-fluorophenyl)piperazin-1-yl]propan-1-amine
  参考文献：
  名称：

  一种交互式SAR方法，用于发现新的杂化硫杂探针，作为亲和力在亚纳摩尔范围内的D2样受体的配体。

  摘要：

  合成了一系列的[（苯基哌嗪基）烷基]-异吲哚-1,3-二酮衍生物，用作多巴胺能受体的探针。在该系列中，化合物6a对D4和D3受体的亲和力最高，Ki值在低纳摩尔范围内，D2 / D4-和D2 / D3-选择性指数分别为72和20。采用最优化回合，得到Ki（D4）值为0.62 nM的D4选择性配体噻吩-2-羧酰胺9a，其丁基类似物10a的Ki（D4）和Ki（D3）值为0.03和0.26 nM。对接实验揭示了独特的D4残基Arg186在操纵配体D4亚型受体选择性中的重要性。

  DOI：

  10.1002/cbdv.201300204
• 作为产物：
  描述：

  邻苯二甲酸亚胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 2-{3-[4-(4-fluorophenyl)piperazin-1-yl]propyl}-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  作为有效和口服活性抗伤害药的芳基哌嗪基烷基吡啶并吡嗪酮及其类似物：合成和作用机理的研究。

  摘要：

  在结构上与先前描述的铅A（5-{[4-（3-氯苯基）哌嗪-1-基]-丙基} -3-甲基-7-苯基异s唑并[4,5-d]哒嗪-合成4-（5H）-一）并测试其镇痛活性。许多受试分子的剂量为20 mg kg-1 po，表现出很高的抗伤害感受活性，尤其是化合物5a，11c，15a，21和22，能够将腹部收缩的数量减少50多种％在扭体测试中。铅A的药理研究使我们阐明了该化合物的作用机理，表明它通过抑制去甲肾上腺素的再摄取而发挥了镇痛作用。用α2-拮抗剂育亨宾预处理可以完全防止某些最有趣的新分子的抗伤害感受，

  DOI：

  10.1021/jm060743g

文献信息

• Substituted cyclic amine compounds as 5HT2 antagonists
  申请人：TOA EIYO LTD.

  公开号：EP0661266A1

  公开（公告）日：1995-07-05

  A substituted cyclic amine compound represented by the following general formula (1) wherein each of R¹ to R⁵ represents a hydrogen atom, a hydroxyl group, an alkyl group or the like, D represents a methine moiety, a nitrogen atom or the like, P represents -CR⁶(R⁷)- or -NR⁸-, Q represents a methine moiety or a nitrogen atom, each of T and B is a single bond or represents a methylene moiety, a carbonyl group or the like, n is an integer of 1 to 6 and each of R⁶, R⁷ and R⁸ represents a hydrogen atom, an alkyl group or the like; and synthetic intermediates thereof. The inventive compound is useful in preventing and treating circulatory organ-related diseases such as hypertension, ischemic heart disease, cerebrovascular disease, peripherol circulatory disease and the like.

  由以下通式（1）代表的取代环胺化合物 其中 R¹ 至 R⁵ 各代表氢原子、羟基、烷基或类似物，D 代表甲基、氮原子或类似物，P 代表-CR⁶(R⁷)- 或-NR⁸-，Q 代表甲基或氮原子、T和B各自为单键或代表亚甲基、羰基或类似基团，n为1至6的整数，R⁶、R⁷和R⁸各自代表氢原子、烷基或类似基团；及其合成中间体。 本发明化合物可用于预防和治疗循环器官相关疾病，如高血压、缺血性心脏病、脑血管疾病、外周循环疾病等。
• Synthesis and biological evaluation of (phenylpiperazinyl-propyl)arylsulfonamides as selective 5-HT2A receptor antagonists
  作者：Euna Yoo、Juhee Yoon、Ae Nim Pae、Hyewhon Rhim、Woo-Kyu Park、Jae Yang Kong、Hea-Young Park Choo

  DOI：10.1016/j.bmc.2009.12.067

  日期：2010.2

  A novel series of 5-HT2A ligands that contain a (phenylpiperazinyl-propyl)arylsulfonamides skeleton was synthesized. Thirty-seven N-(cycloalkylmethyl)-4-methoxy-N-(3-(4-arylpiperazin-1-yl)propyl)arylsulfonamide and N-(4-(4-arylpiperazin-1-yl)butan-2-yl)-arylsulfonamide compounds were obtained. The binding of these compounds to the 5-HT2A, 5-HT2C, and 5-HT7 receptors was evaluated. Most of the compounds showed IC50 values of less than 100 nM and exhibited high selectivity for the 5-HT2A receptor. Among the synthesized compounds, 16a and 16d showed good affinity at 5-HT2A (IC50 = 0.7 nM and 0.5 nM) and good selectivity over 5-HT2C (50-100 times) and 5-HT7 (1500-3000 times). (C) 2010 Elsevier Ltd. All rights reserved.
• Further optimization of novel pyrrole 3-carboxamides for targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant
  作者：Suk Youn Kang、Eun-Jung Park、Woo-Kyu Park、Hyun Jung Kim、Gildon Choi、Myung Eun Jung、Hee Jeong Seo、Min Ju Kim、Ae Nim Pae、Jeongmin Kim、Jinhwa Lee

  DOI：10.1016/j.bmc.2010.06.037

  日期：2010.8

  In the continuing search for novel compounds targeting serotonin 5-HT2A, 5-HT2C, and serotonin transporter, new arylpiperazine-containing pyrrole 3-carboxamide derivatives were synthesized and evaluated. Based on the lead reported previously, structural modifications regarding N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)-1,2-dimethyl-5-phenyl-1H-pyrrole-3-carboxamide 5, were accomplished for improvements in not only binding affinity against serotonin receptors and transporter, but also in hERG channel inhibition. Along the line, both the forced swimming tests and spontaneous locomotor activity tests were performed to distinguish between antidepressant activity and false positive results. As potential antidepressant agents, both 2,4-dimethyl-5-phenyl-1H-pyrrole-3-carboxamide and 5-tert-butyl-2-methyl-1H-pyrrole-3-carboxamide derivatives exhibited favorable in vitro and in vivo activities, warranting further investigation around these scaffolds. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of oxazole derivatives as T-type calcium channel blockers
  作者：Jie Eun Lee、Hun Yeong Koh、Seon Hee Seo、Yi Yeon Baek、Hyewhon Rhim、Yong Seo Cho、Hyunah Choo、Ae Nim Pae

  DOI：10.1016/j.bmcl.2010.05.030

  日期：2010.7

  T-type calcium channel is one of therapeutic targets for the treatment of cardiovascular diseases and neuropathic pain. In this study, as a part of our ongoing efforts to develop potent T-type calcium channel blockers, we designed oxazole derivatives substituted with arylpiperazinylalkylamines. The oxazoles were synthesized in a convenient convergent synthetic method, and biologically evaluated against alpha(1G) (Ca(V)3.1) T-type calcium channel. Among total 41 oxazole compounds synthesized, the most active one was the compound 10-35 with an IC(50) value of 0.65 mu M, which is comparable with that of mibefradil. (C) 2010 Elsevier Ltd. All rights reserved.
• Arylpiperazinylalkylpyridazinones and Analogues as Potent and Orally Active Antinociceptive Agents:  Synthesis and Studies on Mechanism of Action
  作者：Nicoletta Cesari、Claudio Biancalani、Claudia Vergelli、Vittorio Dal Piaz、Alessia Graziano、Pierfrancesco Biagini、Carla Ghelardini、Nicoletta Galeotti、Maria Paola Giovannoni

  DOI：10.1021/jm060743g

  日期：2006.12.1

  arylpiperazinylalkylpyridazinones structurally related to the previously described lead A (5-[4-(3-chlorophenyl)piperazin-1-yl]-propyl}-3-methyl-7-phenylisossazolo[4,5-d] pyridazin-4-(5H)-one) were synthesized and tested for their analgesic activity. Many of the tested molecules, at the dose of 20 mg kg-1 p.o., showed high antinociceptive activity, in particular, compounds 5a, 11c, 15a, 21 and 22, which were

  在结构上与先前描述的铅A（5-[4-（3-氯苯基）哌嗪-1-基]-丙基} -3-甲基-7-苯基异s唑并[4,5-d]哒嗪-合成4-（5H）-一）并测试其镇痛活性。许多受试分子的剂量为20 mg kg-1 po，表现出很高的抗伤害感受活性，尤其是化合物5a，11c，15a，21和22，能够将腹部收缩的数量减少50多种％在扭体测试中。铅A的药理研究使我们阐明了该化合物的作用机理，表明它通过抑制去甲肾上腺素的再摄取而发挥了镇痛作用。用α2-拮抗剂育亨宾预处理可以完全防止某些最有趣的新分子的抗伤害感受，