N¹-(((R)-4-benzylpiperazin-2-yl)methyl)-N¹-((S)-5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine | 1380336-22-0

• 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: N¹-(((R)-4-benzylpiperazin-2-yl)methyl)-N¹-((S)-5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine
• 英文别名: N1-(((R)-4-benzylpiperazin-2-yl)methyl)-N1-((S)-5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine；N'-[[(2R)-4-benzylpiperazin-2-yl]methyl]-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
• CAS: 1380336-22-0
• 化学式: C₂₅H₃₇N₅
• 分子量: 407.602
• InChiKey: FSFDEFLPJSVACO-RPWUZVMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  57.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-Boc-哌嗪-2-羧酸 在 sodium tetrahydroborate 、 calcium(II) chloride dihydrate 、 水 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 88.0h， 生成 N¹-(((R)-4-benzylpiperazin-2-yl)methyl)-N¹-((S)-5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine
  参考文献：
  名称：

  新型N-芳基哌嗪CXCR4拮抗剂的发现

  摘要：

  描述了具有取代的哌嗪作为苯并咪唑替代物的一系列新的CXCR4拮抗剂。这些化合物在CXCR4介导的功能和HIV检测中显示出微摩尔至纳摩尔的效价，即在MAGI-CCR5 / CXCR4细胞中抑制X4 HIV-1 IIIB病毒和在Schem- 1细胞中抑制SDF-1诱导的钙释放。SAR的初步研究导致鉴定出一系列N-芳基哌嗪为最有效的化合物。结果表明，SAR表示芳香环的类型和位置，以及接头和立体化学的类型对于活性均很重要。对几种先导化合物进行分析表明，一种（49b）降低了对CYP450和hERG的敏感性，同时考虑了SDF-1和HIV效力（6–20 nM）时获得了最佳的总体特征。

  DOI：

  10.1016/j.bmcl.2015.04.036

文献信息

• FUSED AZINES AS CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USES RELATED THERETO
  申请人：Emory University

  公开号：EP3153510B1

  公开（公告）日：2020-05-06
• USE OF DIANHYDROGALACTITOL AND ANALOGS OR DERIVATIVES THEREOF IN COMBINATION WITH PLATINUM-CONTAINING ANTINEOPLASTIC AGENTS TO TREAT NON-SMALL-CELL CARCINOMA OF THE LUNG AND BRAIN METASTASES
  申请人：Del Mar Pharmaceuticals

  公开号：US20160008316A1

  公开（公告）日：2016-01-14

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N 7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents and can possess additive or super-additive effects.
• USE OF DIANHYDROGALACTITOL AND ANALOGS OR DERIVATIVES THEREOF IN COMBINATION WITH PLATINUM-CONTAINING ANTINEOPLASTIC AGENTS TO TREAT NON-SMALL-CELL CARCINOMA OF THE LUNG AND BRAIN METASTASES
  申请人：BACHA Jeffrey

  公开号：US20180140571A1

  公开（公告）日：2018-05-24

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of non-small-cell lung carcinoma (NSCLC) and ovarian cancer, as well as other types of malignancy, including brain metastases of NSCLC. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N 7 methylation. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents and can possess additive or super-additive effects.
• Discovery of novel N-aryl piperazine CXCR4 antagonists
  作者：Huanyu Zhao、Anthony R. Prosser、Dennis C. Liotta、Lawrence J. Wilson

  DOI：10.1016/j.bmcl.2015.04.036

  日期：2015.11

  A novel series of CXCR4 antagonists with substituted piperazines as benzimidazole replacements is described. These compounds showed micromolar to nanomolar potency in CXCR4-mediated functional and HIV assays, namely inhibition of X4 HIV-1IIIB virus in MAGI-CCR5/CXCR4 cells and inhibition of SDF-1 induced calcium release in Chem-1 cells. Preliminary SAR investigations led to the identification of a

  描述了具有取代的哌嗪作为苯并咪唑替代物的一系列新的CXCR4拮抗剂。这些化合物在CXCR4介导的功能和HIV检测中显示出微摩尔至纳摩尔的效价，即在MAGI-CCR5 / CXCR4细胞中抑制X4 HIV-1 IIIB病毒和在Schem- 1细胞中抑制SDF-1诱导的钙释放。SAR的初步研究导致鉴定出一系列N-芳基哌嗪为最有效的化合物。结果表明，SAR表示芳香环的类型和位置，以及接头和立体化学的类型对于活性均很重要。对几种先导化合物进行分析表明，一种（49b）降低了对CYP450和hERG的敏感性，同时考虑了SDF-1和HIV效力（6–20 nM）时获得了最佳的总体特征。