6-(piperazin-1-yl)phenanthridine | 1173517-33-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-(piperazin-1-yl)phenanthridine
• 英文别名: 6-Piperazinophenanthridine；6-piperazin-1-ylphenanthridine
• CAS: 1173517-33-3
• 化学式: C₁₇H₁₇N₃
• 分子量: 263.342
• InChiKey: CHRKYIPLMABLPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(piperazin-1-yl)phenanthridine 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 反应 4.5h， 生成 6-(4-((1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)phenanthridine
  参考文献：
  名称：

  设计，合成和评价6-（4-（（取代的-1 H -1,2,3-三唑-4-基）甲基）哌嗪-1-基）菲啶类似物作为分枝杆菌药

  摘要：

  本信的重点是设计和合成一系列十九种新的使用（6-（4-（（取代的-1 H -1,2,3-三唑-4-基）甲基）哌嗪-1-基）菲啶类似物的6-（4-（（（取代的-1 H -1,2,3-三唑-4-基）甲基）哌嗪-1-基）菲啶类似物单击化学，并评估其对结核分枝杆菌H 37 Rv的抗结核活性。在测试的化合物中，7f和7j表现出良好的活性（MIC = 3.125μg/ mL），而8a表现出优异的活性（MIC = 1.56μg/ mL），对结核分枝杆菌H 37 Rv的生长具有抑制作用。此外，7f，7j和8a对化合物进行了针对小鼠巨噬细胞（RAW264.7）细胞系的细胞毒性研究，其选择性指数值大于15，表明该化合物适用于进一步的药物开发。

  DOI：

  10.1016/j.bmcl.2013.10.016
• 作为产物：
  描述：

  6(5H)-菲啶酮 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-(piperazin-1-yl)phenanthridine
  参考文献：
  名称：

  使用 DMF 作为 C1 源的 2-芳基苯胺的环境温度脱氢 C(Ar)–H 羰基内酰胺化

  摘要：

  报道了由可见光和钾碱促进的 2-芳基苯胺的直接脱氢 C-H 裂解羰基内酰胺化。在没有氧化剂的情况下，溶剂 DMF 充当唯一的羰基来源。氢气的不可逆释放将此反应拖向稳定的菲啶酮产物。这项工作提供了将广泛的 2-芳基苯胺直接转化为各种菲啶酮的方法。该方法可应用于生物活性分子和有机光电材料的合成。

  DOI：

  10.1021/acs.orglett.3c00585

文献信息

• Design and Synthesis of Piperazinylpyridine Derivatives as Novel 5-HT1A Agonists/5-HT3 Antagonists for the Treatment of Irritable Bowel Syndrome (IBS)
  作者：Akira Asagarasu、Teruaki Matsui、Hiroyuki Hayashi、Satoru Tamaoki、Yukinao Yamauchi、Michitaka Sato

  DOI：10.1248/cpb.57.34

  日期：——

  We have prepared a series of piperazinylpyridine derivatives for the treatment of irritable bowel syndrome (IBS). These compounds, which were designed by pharmacophore analysis, bind to both serotonin subtype 1A (5-HT1A) and subtype 3 (5-HT3) receptors. The nitrogen atom of the isoquinoline, a methoxy group and piperazine were essential to the pharmacophore for binding to these receptors. We also synthesized furo- and thienopyridine derivatives according to structure–activity relationship analyses. Compound 17c (TZB-20810) had high affinities to these receptors and exhibited 5-HT1A agonistic activity and 5-HT3 antagonistic activity concurrently, and is a promising drug for further development in the treatment of IBS.

  我们已准备了一系列哌嗪吡啶衍生物用于治疗肠易激综合征（IBS）。这些化合物通过药效团分析设计，能够同时与血清素亚型1A（5-HT1A）和亚型3（5-HT3）受体结合。异喹啉的氮原子、一个甲氧基和哌嗪是与这些受体结合的药效团的重要组成部分。我们还根据结构-活性关系分析合成了呋喃和噻吡啶衍生物。化合物17c（TZB-20810）对这些受体具有很高的亲和力，同时展现出5-HT1A激动剂活性和5-HT3拮抗剂活性，是治疗IBS方面具有进一步开发潜力的有前景药物。
• Synthesis and evaluation of anti-tubercular activity of 6-(4-substitutedpiperazin-1-yl) phenanthridine analogues
  作者：Hunsur Nagendra Nagesh、Narva Suresh、Kalaga Mahalakshmi Naidu、Boyineni Arun、Jonnalagadda Padma Sridevi、Dharmarajan Sriram、Perumal Yogeeswari、Kondapalli Venkata Gowri Chandra Sekhar

  DOI：10.1016/j.ejmech.2014.01.005

  日期：2014.3

  A series of seventeen new 6-(4-substitutedpiperazin-1-yl)phenanthridine derivatives were designed, synthesized, and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H(37)Rv by Microplate Alamar Blue Assay and most active compounds were tested for cytotoxicity studies against mouse macrophage cell lines (RAW264.7). Among the tested compounds, ten compounds exhibited significant activity against the growth of M. tuberculosis (MIC ranging from 1.56 to 6.25 mu g/mL). In particular, compounds 5e, 5j and 5k displayed excellent activity against the growth of M. tuberculosis (MIC 1.56 mu g/mL). The selectivity index values were found to be > 25, indicating compounds likeliness in drug development for tuberculosis. The structure of 5k is substantiated by X-ray crystallographic study. Structure activity correlation indicates the importance of substituent at 4th position of piperazinyl phenanthridine ring. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Novel amide and sulphonamide derivatives of 6-(piperazin-1-yl)phenanthridine as potent Mycobacterium tuberculosis H37Rv inhibitors
  作者：Kalaga Mahalakshmi Naidu、Hunsur Nagendra Nagesh、Manjeet Singh、Dharmarajan Sriram、Perumal Yogeeswari、Kondapalli Venkata Gowri Chandra Sekhar

  DOI：10.1016/j.ejmech.2015.01.013

  日期：2015.3

  A series of thirty three novel 6-(piperazin-1-yl)phenanthridine amide and sulphonamide analogues were synthesized, characterized and screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis (MTB) H37Rv strain. These compounds exhibited minimum inhibitory concentration (MIC) between 1.56 and >= 50 mu g/mL. Out of these derivatives, few compounds 61, 6r, 7b, 7f, 7g and 7k exhibited moderate activity (MIC = 6,25 mu g/mL) and compounds 6b, 6e, 6k, 6n, 7h, 7i and 7n displayed good activity (MIC = 3.13 mu g/mL), whereas compounds 6m, 6s and 7d exhibited excellent anti-tubercular activity (MIC = 1.56 mu g/mL). In addition, MIT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the toxicity profile of the newly synthesized compounds and selectivity index of the compounds was determined. Additionally, compounds 6b and 7d were docked to the ATPase domain of M. tuberculosis GyrB protein to know the interaction profile and structures of compounds 6b and 7d were further substantiated through single crystal XRD. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Discovery of a Novel 5-HT₃ Antagonist/5-HT_1A Agonist 3-Amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}quinazolin-4(3<i>H</i>)-one (TZB-30878) as an Orally Bioavailable Agent for Irritable Bowel Syndrome
  作者：Akira Asagarasu、Teruaki Matsui、Hiroyuki Hayashi、Satoru Tamaoki、Yukinao Yamauchi、Kouichi Minato、Michitaka Sato

  DOI：10.1021/jm1002292

  日期：2010.11.11

  We have prepared a series of quinazolinone derivatives linked with piperazinylquinoline for the treatment of irritable bowel syndrome (IBS). Using pharmacophore analysis, we designed and synthesized compounds which bind to both serotonin receptor subtype 1A (5-HT1A) and subtype 3 (5-HT3). Quinazolinone derivatives with a sulfur atom in the linker showed high affinity in in vitro assays, but low in vivo activity. Focusing on the linker to improve the pharmacokinetic profile, the sulfur atom in the linker was replaced with a methylene group. Further optimization led to the discovery of compound 17m (TZB-30878) (J. Pharmacol. Exp. Ther. 2007, 322, 1315-1323, Patent WO2005082887 (A1), 2005), a novel 5-HT1A agonist/5-HT3 antagonist in the 3-aminoquinazolinone series. In in vivo functional assays, 17m dose dependently inhibited the Bezold-Jarisch reflex and induced 5-HT1A-mediated behaviors, and in an IBS animal model, 17m significantly inhibited stress-induced defecation. Pretreatment by WAY-100635 (5-HT1A antagonist) significantly attenuated but did not abolish the inhibitory effects of 17m. These results suggested that 17m exerted inhibitory effects via both 5-HT1A agonistic and 5-HT3 antagonistic activities and that 17m would be useful as a therapeutic agent for IBS.
• Design, synthesis and evaluation of 6-(4-((substituted-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)phenanthridine analogues as antimycobacterial agents
  作者：Hunsur Nagendra Nagesh、Kalaga Mahalakshmi Naidu、Damarla Harika Rao、Jonnalagadda Padma Sridevi、Dharmarajan Sriram、Perumal Yogeeswari、Kondapalli Venkata Gowri Chandra Sekhar

  DOI：10.1016/j.bmcl.2013.10.016

  日期：2013.12

  Focus in this Letter is made to design and synthesize a series of nineteen new 6-(4-((substituted-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl)phenanthridine analogues employing click chemistry and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 7f and 7j exhibited good activity (MIC = 3.125 μg/mL), while 8a displayed excellent activity

  本信的重点是设计和合成一系列十九种新的使用（6-（4-（（取代的-1 H -1,2,3-三唑-4-基）甲基）哌嗪-1-基）菲啶类似物的6-（4-（（（取代的-1 H -1,2,3-三唑-4-基）甲基）哌嗪-1-基）菲啶类似物单击化学，并评估其对结核分枝杆菌H 37 Rv的抗结核活性。在测试的化合物中，7f和7j表现出良好的活性（MIC = 3.125μg/ mL），而8a表现出优异的活性（MIC = 1.56μg/ mL），对结核分枝杆菌H 37 Rv的生长具有抑制作用。此外，7f，7j和8a对化合物进行了针对小鼠巨噬细胞（RAW264.7）细胞系的细胞毒性研究，其选择性指数值大于15，表明该化合物适用于进一步的药物开发。