1-(2-methoxyphenyl)-4-(but-3-yn-1-yl)-piperazine | 1297273-59-6

• 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: 1-(2-methoxyphenyl)-4-(but-3-yn-1-yl)-piperazine
• 英文别名: 1-(but-3-yn-1-yl)-4-(2-methoxyphenyl)piperazine；1-(2-methoxyphenyl)-4-(but-3-ynyl)piperazine；1-But-3-ynyl-4-(2-methoxyphenyl)piperazine
• CAS: 1297273-59-6
• 化学式: C₁₅H₂₀N₂O
• mdl: MFCD18535635
• 分子量: 244.337
• InChiKey: VAXUXPGDIBCBCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  15.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-methoxyphenyl)-4-(but-3-yn-1-yl)-piperazine 在 copper(ll) sulfate pentahydrate 、 硫酸 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 18.0h， 生成 5-(4-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}triazol-1-yl)pyrazolo[1,5-a]pyridine
  参考文献：
  名称：

  1,4-Disubstituted aromatic piperazines with high 5-HT2A/D2 selectivity: Quantitative structure-selectivity investigations, docking, synthesis and biological evaluation

  摘要：

  Simultaneous targeting of dopamine D-2 and 5-HT2A receptors for the treatment of schizophrenia is one key feature of typical and atypical antipsychotics. In most of the top-selling antipsychotic drugs like aripiprazole and risperidone, high affinity to both receptors can be attributed to the presence of 1,4-disubstituted aromatic piperazines or piperidines as primary receptor recognition elements. Taking advantage of our in-house library of phenylpiperazine-derived dopamine receptor ligands and experimental data, we established highly significant CoMFA and CoMSIA models for the prediction of 5-HT2A over D-2 selectivity. Subsequently, the models were applied to identify the selective candidates 55-57 from our newly synthesized library of GPCR ligands comprising a pyrazolo[1,5-a]pyridine head group and a 1,2,3-triazole based linker unit. The test compound 57 showed subnanomolar a K-i value (0.64 nM) for 5-HT2A and more than 10- and 30-fold selectivity over the dopamine receptor isoforms D-2S and D-2L, respectively. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.050
• 作为产物：
  描述：

  1-(2-甲氧苯基)哌嗪 、 对甲苯磺酸 3-丁炔酯 在 potassium carbonate 、 sodium iodide 作用下， 以 丙酮 为溶剂， 以90%的产率得到1-(2-methoxyphenyl)-4-(but-3-yn-1-yl)-piperazine
  参考文献：
  名称：

  Further SAR study on 11-O-substituted aporphine analogues: Identification of highly potent dopamine D3 receptor ligands

  摘要：

  A series of new aporphine analogues (aporlogues) were prepared from appropriate aporphine precursors and arylpiperazines using the Click reaction protocol. These compounds displayed good to high affinity at the D-3 receptor, low or no affinity at the D-1 and D-2 receptors. Compounds 7f and 11c stood out as the most potent at the D-3 receptor among our newly synthesized aporlogues with K-i values of 2.67 and 1.14 nM, respectively. Further assay at the 5-HT1A receptor revealed that aporlogues 7f and 11c also showed high affinity at this receptor with K-i values of 9.68 and 7.59 nM, respectively. They were 3.6- and 6.6-fold more potent at the D-3 over 5-HT1A receptors. Such D-3/5-HT1A dual property of these compounds may be useful in the treatment of several brain disorders. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.01.053

文献信息

• Development of a Focused Library of Triazole-Linked Privileged-Structure-Based Conjugates Leading to the Discovery of Novel Phenotypic Hits against Protozoan Parasitic Infections
  作者：Elisa Uliassi、Lorna Piazzi、Federica Belluti、Andrea Mazzanti、Marcel Kaiser、Reto Brun、Carolina B. Moraes、Lucio H. Freitas-Junior、Sheraz Gul、Maria Kuzikov、Bernhard Ellinger、Chiara Borsari、Maria Paola Costi、Maria Laura Bolognesi

  DOI：10.1002/cmdc.201700786

  日期：2018.4.6

  to generate a focused library of high‐quality compounds. The versatility of this approach was combined with the feasibility of a phenotypic assay, integrated with early ADME‐tox profiling. Thus, an 18‐membered library was efficiently assembled via Huisgen cycloaddition of phenothiazine, biphenyl, and phenylpiperazine scaffolds. The resulting 18 compounds were then tested against seven parasite strains

  疟原虫，利什曼原虫和锥虫引起的原生动物感染spp。对全世界的传染病负担做出重大贡献，导致严重的发病率和死亡率。现有治疗方法的不足要求进行具有成本效益和时间效益的药物开发。为此，我们设想将特权结构的三唑键连接作为有效的药物设计策略，以生成高质量化合物的重点文库。这种方法的多功能性与表型分析的可行性相结合，并与早期的ADME-tox分析相结合。因此，通过吩噻嗪，联苯和苯基哌嗪支架的Huisgen环加成反应，可以有效地组装一个由18个成员组成的文库。然后对所得的18种化合物针对7种寄生虫菌株进行了测试，并针对两种哺乳动物细胞系进行了反筛选。平行地，h评估了ERG和细胞色素P450（CYP）的抑制作用以及线粒体毒性。值得注意的是，10-（（1-（3-（[[1,1'-联苯] -3-基氧基）丙基）-1 H -1,1,2,3-三唑-5-基）甲基）-10 H-吩噻嗪（7）和10-（3-（1-（3-（[[1