2-(3-(4-(3-chlorophenyl)-piperazin-1-yl)-propyl)-isoindoline-1,3-dione | 25557-35-1

• 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: 2-(3-(4-(3-chlorophenyl)-piperazin-1-yl)-propyl)-isoindoline-1,3-dione
• 英文别名: N-{3-[4-(3-chloro-phenyl)-piperazin-1-yl]-propyl}-phthalimide；N-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]phthalimide；2-[3-[4-(3-Chlorophenyl)piperazin-1-yl]propyl]isoindole-1,3-dione
• CAS: 25557-35-1
• 化学式: C₂₁H₂₂ClN₃O₂
• 分子量: 383.878
• InChiKey: ZQFOZNXXHQKNBF-UHFFFAOYSA-N

物化性质

• 沸点：
  555.4±50.0 °C(Predicted)
• 密度：
  1.290±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 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：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-(4-(3-chlorophenyl)-piperazin-1-yl)-propyl)-isoindoline-1,3-dione 在 肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以90%的产率得到1-(3-氨基-1-丙基)-4-(3-氯苯基)哌嗪
  参考文献：
  名称：

  UNC119-货物相互作用的小分子抑制。

  摘要：

  N-末端肉豆蔻酰化促进膜的结合和蛋白质（特别是Src家族激酶）的活性，但是其潜在机制才刚刚被人们理解。伴侣UNC119A / B调节N-肉豆蔻酰化蛋白的细胞分布和信号传导。UNC119-货物相互作用的选择性小分子调节剂将是无价的工具，但尚未有报道。我们在此报告了第一个UNC119-货物相互作用抑制剂squarunkin A的开发。SquarunkinA用IC 50选择性抑制代表Src激酶N端的肉豆蔻酰化肽与UNC119A的结合值为10 nm。它与细胞裂解物中的UNC119蛋白结合，并干扰Src激酶的激活。我们的研究结果表明，对UNC119-货物相互作用的小分子抑制可能为调节Src激酶的活性提供新的机会，而Src激酶的活性与直接抑制酶激酶的活性无关。

  DOI：

  10.1002/anie.201701905
• 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-(3-chlorophenyl)-piperazin-1-yl)-propyl)-isoindoline-1,3-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

• Isoindolinyl-alkyl-piperazines
  申请人：Bristol-Myers Company

  公开号：US04585773A1

  公开（公告）日：1986-04-29

  The invention is generally concerned with isoindolinyl-alkylpiperazine compounds generally characterized by the formula ##STR1## wherein X is halogen or trifluoromethyl; n is an integer ranging from 2 to 5; Y is ##STR2## in which R.sub.1 is hydrogen, halogen, lower alkyl, lower alkoxy, trifluoromethyl, cyano; R.sub.2 is hydrogen, halogen, lower alkyl, lower alkoxy; and R.sub.3 is hydrogen, cyano. These compounds are useful as diuretic and/or antihypertensive agents.

  这项发明通常涉及isoindolinyl-烷基哌嗪化合物，一般以以下式子为特征：##STR1## 其中X是卤素或三氟甲基；n是一个从2到5的整数；Y是##STR2## 其中R.sub.1是氢、卤素、较低烷基、较低烷氧基、三氟甲基、氰基；R.sub.2是氢、卤素、较低烷基、较低烷氧基；R.sub.3是氢、氰基。这些化合物可用作利尿剂和/或降压药。
• Synthesis, computational simulations and biological evaluation of new dual 5HT1A/5HT7 receptor ligands based on purine-2,6-dione scaffold
  作者：Agnieszka Zagórska、Anna Partyka、Magdalena Jastrzębska-Więsek、Anna Czopek、Monika Fryc、Agata Siwek、Monika Głuch-Lutwin、Barbara Mordyl、Anna Maślanka、Anna Jaromin、Rafał Kurczab

  DOI：10.1016/j.bioorg.2023.106737

  日期：2023.10

  experimentally established physicochemical parameters of compound 11 showed that compound, as slightly ionized in the blood, could penetrate the blood–brain barrier. A molecular docking study showed that the fluorine substitution introduces additional stabilization effects on binding to 5HT1A/5HT7Rs. In animal assays of depression and anxiety, compound 11 revealed activity in terms of dosage compared to marketed

  新的双5HT 1A /5HT 7受体配体是基于带有氟原子的嘌呤-2,6-二酮支架设计的。合成了21个新衍生物，并总结了它们的构效关系。化合物11 (7-(2-(3-氟苯基)-2-氧代乙基)-8-((4-(4-(2-甲氧基苯基)哌嗪-1-基)丁基)氨基)-1,3-二甲基- 3,7-二氢-1H-嘌呤-2,6-二酮）对 5HT 1A R 和 5HT 7 R 表现出最高的亲和力，并且是 5-HT 1A R 最有效的拮抗剂（ K b = 0.26 ± 0.1 nM）其活性可以参考参考化合物 NAN-190 ( K b = 0.26 ± 0.1 nM)。实验确定的化合物11的理化参数表明，该化合物在血液中轻微电离，可以穿透血脑屏障。分子对接研究表明，氟取代对 5HT 1A /5HT 7 R 的结合引入了额外的稳定作用。在抑郁和焦虑的动物试验中，与市售精神药物（如氟西汀、西酞普兰和舍曲林）相比，化合物11在剂量方面显示出活性。
• Identification of novel PD-1/PD-L1 small molecule inhibitors: virtual screening, synthesis and in vitro characterisation
  作者：Tingting Wu、Hu Cheng、Lijie Sima、Zhongyuan Wang、Weiwei Ouyang、Jianta Wang、Yunlei Hou、Dongsheng Zhao、Weike Liao、Chujiao Hu

  DOI：10.1080/14756366.2024.2353711

  日期：2024.12.31

  The PD-1/PD-L1 pathway is considered as one of the most promising immune checkpoints in tumour immunotherapy. However, researchers are faced with the inherent limitations of antibodies, driving the...

  PD-1/PD-L1 通路被认为是肿瘤免疫治疗中最有前途的免疫检查点之一。然而，研究人员面临着抗体的固有局限性，推动了...
• 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.