2-{3-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl}isoindole-1,3-dione | 1220831-49-1

• 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-(2,3-dimethylphenyl)piperazin-1-yl]propyl}isoindole-1,3-dione
• 英文别名: 2-[3-[4-(2,3-Dimethylphenyl)piperazin-1-yl]propyl]isoindole-1,3-dione
• CAS: 1220831-49-1
• 化学式: C₂₃H₂₇N₃O₂
• 分子量: 377.486
• InChiKey: FNSNBIJCWWZDQE-UHFFFAOYSA-N

物化性质

• 沸点：
  556.0±50.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 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-(2,3-dimethylphenyl)piperazin-1-yl]propyl}isoindole-1,3-dione 在 盐酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 22.0h， 生成 2-N-[3-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl]-4-N-(furan-2-ylmethyl)quinazoline-2,4-diamine
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,4-diaminoquinazoline derivatives as novel heat shock protein 90 inhibitors

  摘要：

  Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.117
• 作为产物：
  描述：

  N-(3-溴丙基)苯二胺 、 1-(2,3-dimethylphenyl)piperazine hydrochloride 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-{3-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl}isoindole-1,3-dione
  参考文献：
  名称：

  Further optimization of novel pyrrole 3-carboxamides for targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2010.06.037

文献信息

• Piperazinylalkylpyrazole derivatives useful as selective T-type calcium channel blockers and preparation method thereof
  申请人：Nam Ghilsoo

  公开号：US20070049604A1

  公开（公告）日：2007-03-01

  The present invention provides for novel piperazinylalkylpyrazole derivatives, the preparation method thereof and the selective T-type calcium channel blocking activity thereof. Particularly, it provides a piperazinylalkylpyrazole derivative as represented by the formula set forth below or its pharmaceutically acceptable salts, and its preparation method thereof. The compound of Formula 1 is a novel piperazinylalkylpyrazole derivative, which particulary has T-type Ca 2+ channel blocking effect and thus can be useful as a therapeutic agent for nerve and muscle pain.

  本发明提供了新型的哌嗪基烷基吡唑衍生物、其制备方法以及选择性T型钙通道阻滞活性。特别地，本发明提供了以下公式所示的哌嗪基烷基吡唑衍生物或其药学上可接受的盐，以及其制备方法。公式1的化合物是一种新型的哌嗪基烷基吡唑衍生物，特别具有T型Ca2+通道阻滞作用，因此可以作为神经和肌肉疼痛的治疗剂。
• 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.
• Arylpiperazine-containing pyrimidine 4-carboxamide derivatives targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant
  作者：Jong Yup Kim、Deukjoon Kim、Suk Youn Kang、Woo-Kyu Park、Hyun Jung Kim、Myung Eun Jung、Eun-Jung Son、Ae Nim Pae、Jeongmin Kim、Jinhwa Lee

  DOI：10.1016/j.bmcl.2010.09.081

  日期：2010.11

  Pyrimidine usually has good pharmacokinetic properties as a drug substance and considerable efforts have been devoted to develop pyrimidine derivatives into drug candidates. Arylpiperazine-containing pyrimidine 4-carboxamide derivatives were synthesized and evaluated for binding to serotonin receptors and transporter. Pyrimidine derivatives showed good antidepressant activity in FST (forced swimming test) animal model and also displayed no appreciable inhibitory activity against hERG channel blocking assay. Herein SAR studies of pyrimidine derivatives targeting serotonin receptors and transporter will be disclosed. (C) 2010 Elsevier Ltd. All rights reserved.
• Arylpiperazine-containing pyrrole 3-carboxamide derivatives 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、Daeyoung Jeong、Myung Eun Jung、Kwang-Seop Song、Suk Ho Lee、Hee Jeong Seo、Min Ju Kim、MinWoo Lee、Ho-Kyun Han、Eun-Jung Son、Ae Nim Pae、Jeongmin Kim、Jinhwa Lee

  DOI：10.1016/j.bmcl.2010.01.093

  日期：2010.3

  Arylpiperzine-containing pyrrole 3-carboxamide derivatives were synthesized and evaluated as novel antidepressant compounds. The various analogues were efficiently prepared and bio-assayed for binding to 5-HT2A, 5-HT2C receptor, and 5-HT transporter. Based on their in vitro and in vivo activities as well as selectivity over other neurotransmitter receptors and PK profiles, 33 and 34 were identified as lead compounds. Consequently, this pyrrole series of compounds appears to be promising enough to warrant further investigation. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of 2,4-diaminoquinazoline derivatives as novel heat shock protein 90 inhibitors
  作者：Dhanaji Achyutrao Thorat、Munikumar Reddy Doddareddy、Seon Hee Seo、Tae-Joon Hong、Yong Seo Cho、Ji-Sook Hahn、Ae Nim Pae

  DOI：10.1016/j.bmcl.2011.01.117

  日期：2011.3

  Novel 2,4-diaminoquinazoline derivatives originating from a virtual screening approach were designed, synthesized and their biological activities as heat shock protein 90 (Hsp90) inhibitors were evaluated. The prepared compounds exhibited significant anti-proliferative activities against DU-145, HT-29, HCT-116, A375P and MCF-7 cancer cell lines. The selected compounds were tested against Her2, a client protein of Hsp90, and showed significant reduction in Her2 protein expression. Compound 6b was found the most potent, reduced Her2 protein expression levels and induced Hsp70 protein expression levels significantly. (C) 2011 Elsevier Ltd. All rights reserved.