5-(4-methylpiperazin-1-yl)-2,4-dinitro-N-pentylaniline | 1580534-55-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-methylpiperazin-1-yl)-2,4-dinitro-N-pentylaniline
• CAS: 1580534-55-9
• 化学式: C₁₆H₂₅N₅O₄
• 分子量: 351.406
• InChiKey: VDZTVVUDFBKAFA-UHFFFAOYSA-N

物化性质

• 沸点：
  532.0±50.0 °C(predicted)
• 密度：
  1.246±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  25.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  104.79
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  5-(4-methylpiperazin-1-yl)-2,4-dinitro-N-pentylaniline 在 palladium 10% on activated carbon 、 甲酸铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 生成 6-(4-methylpiperazin-1-yl)-2-(5-nitrofuran-2-yl)-1-pentyl-1H-benzo[d]imidazol-5-amine
  参考文献：
  名称：

  Benzimidazole-based compounds kill Mycobacterium tuberculosis

  摘要：

  Tuberculosis remains one of the deadliest infectious diseases, killing 1.4 million people annually and showing a rapid increase in cases resistant to multiple drugs. New antibiotics against tuberculosis are urgently needed. Here we describe the design, synthesis and structure activity relationships of a series of benzimidazole-based compounds with activity against Mycobacterium tuberculosis (Mtb) in a replicating state, a physiologically-induced non-replicating state, or both. Compounds 49, 67, 68, 69, 70, and 72, which shared a 5-nitrofuranyl moiety, exhibited high potency and acceptable selectivity indices (SI). As illustrated by compound 70 (MIC90 < 0.049 mu g/mL, SI > 512), the 5-nitrofuranyl group was compatible with minimal cytotoxicity and good intra-macrophage killing, although it lacked non-replicating activity when assessed by CFU assays. Compound 70 had low mutagenic potential by SOS Chromotest assay, making this class of compounds good candidates for further evaluation and target identification. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.039
• 作为产物：
  描述：

  N-甲基哌嗪 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 5-(4-methylpiperazin-1-yl)-2,4-dinitro-N-pentylaniline
  参考文献：
  名称：

  Benzimidazole-based compounds kill Mycobacterium tuberculosis

  摘要：

  Tuberculosis remains one of the deadliest infectious diseases, killing 1.4 million people annually and showing a rapid increase in cases resistant to multiple drugs. New antibiotics against tuberculosis are urgently needed. Here we describe the design, synthesis and structure activity relationships of a series of benzimidazole-based compounds with activity against Mycobacterium tuberculosis (Mtb) in a replicating state, a physiologically-induced non-replicating state, or both. Compounds 49, 67, 68, 69, 70, and 72, which shared a 5-nitrofuranyl moiety, exhibited high potency and acceptable selectivity indices (SI). As illustrated by compound 70 (MIC90 < 0.049 mu g/mL, SI > 512), the 5-nitrofuranyl group was compatible with minimal cytotoxicity and good intra-macrophage killing, although it lacked non-replicating activity when assessed by CFU assays. Compound 70 had low mutagenic potential by SOS Chromotest assay, making this class of compounds good candidates for further evaluation and target identification. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.039

文献信息

• Discovery, Optimization, and Evaluation of Novel <i>N</i>-(Benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine Analogues as Potent STAT3 Inhibitors for Cancer Treatment
  作者：Ru Wang、Ting-Ting Du、Wen-Qiang Liu、Yi-Chen Liu、Ya-Dong Yang、Jin-Ping Hu、Ming Ji、Bei-Bei Yang、Li Li、Xiao-Guang Chen

  DOI：10.1021/acs.jmedchem.3c00863

  日期：2023.9.14

  reporter cells. After optimization of lead compound 12, compound 40 was identified as a selective STAT3 inhibitor that directly binds the SH2 domain to inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. Compound 40 exhibited antiproliferative activities against STAT3-overactivated DU145 (IC50 value = 2.97 μM) and MDA-MB-231 (IC50 value = 3.26 μM) cancer cells and induced cell

  信号转导子和转录激活子 3 (STAT3) 是癌症治疗的一个有吸引力的靶点。然而，鉴定具有药物样特性的有效且选择性的 STAT3 小分子抑制剂仍然具有挑战性。基于支架组合策略，设计了具有新型N- (苯并咪唑-5-基)-1,3,4-噻二唑-2-胺支架的化合物，及其对白细胞介素6 (IL-6)/JAK的抑制作用/STAT3 通路在 HEK-Blue IL-6 报告细胞中进行了测试。对先导化合物12进行优化后，化合物40被鉴定为选择性 STAT3 抑制剂，可直接结合 SH2 结构域，抑制 STAT3 磷酸化、易位和下游基因转录。化合物40对STAT3过度激活的DU145（IC 50值= 2.97 μM）和MDA-MB-231（IC 50值= 3.26 μM）癌细胞表现出抗增殖活性，并诱导细胞周期停滞和凋亡。在DU145异种移植模型中，腹腔给药后化合物40显示出体内抗肿瘤功效，50 mg/kg时肿瘤生长抑制率为65