2-<2-Dimethylamino-aethylamino>-5-nitro-anilin | 56756-68-4

• 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: 2-<2-Dimethylamino-aethylamino>-5-nitro-anilin
• 英文别名: 1-N-[2-(dimethylamino)ethyl]-4-nitrobenzene-1,2-diamine
• CAS: 56756-68-4
• 化学式: C₁₀H₁₆N₄O₂
• 分子量: 224.263
• InChiKey: DVKKJQAJHKONEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  87.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-<2-Dimethylamino-aethylamino>-5-nitro-anilin 在 palladium 10% on activated carbon 、 氢气 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 三氯化磷 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 反应 92.0h， 生成 N-(1-(2-(dimethylamino)ethyl)-2-(4-ethoxybenzyl)-1H-benzo[d]imidazol-5-yl)thiophen-2-carboximidamide
  参考文献：
  名称：

  NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity

  摘要：

  A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the mu-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the mu-opioid GPCR was predicated on the modulatory role of nitric oxide on mu-opioid receptor function. Structure activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 mu M), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent mu-opioid binding affinity, K-i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 mu M). This work represents a novel approach in the development of new analgesics for the treatment of pain.

  DOI：

  10.1021/ml200268w
• 作为产物：
  描述：

  N'-(2,4-dinitrophenyl)-N,N-dimethylethane-1,2-diamine 在 ammonium sulfide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.5h， 以70.2%的产率得到2-<2-Dimethylamino-aethylamino>-5-nitro-anilin
  参考文献：
  名称：

  NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity

  摘要：

  A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the mu-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the mu-opioid GPCR was predicated on the modulatory role of nitric oxide on mu-opioid receptor function. Structure activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 mu M), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent mu-opioid binding affinity, K-i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 mu M). This work represents a novel approach in the development of new analgesics for the treatment of pain.

  DOI：

  10.1021/ml200268w

文献信息

• Substituted benzimidazole compounds with dual NOS inhibitory activity and mu opioid agonist activity
  申请人：Renton Paul

  公开号：US20080214613A1

  公开（公告）日：2008-09-04

  The present invention relates to benzimidazole compounds having dual nitric oxide synthase (NOS) inhibitory activity and agonist activity at the mu-opioid receptor, to pharmaceutical and diagnostic compositions containing them, and to their medical use, particularly as compounds for the treatment or prevention of chronic pain, acute pain, migraine, and neuropathic pain.

  本发明涉及具有双重一氧化氮合酶（NOS）抑制活性和μ-阿片受体激动活性的苯并咪唑化合物，以及包含它们的药物和诊断组合物，以及它们的医学用途，特别是作为治疗或预防慢性疼痛、急性疼痛、偏头痛和神经病性疼痛的化合物。
• Design, synthesis, and antitumor activity evaluation of potent fourth-generation EGFR inhibitors for treatment of Osimertinib resistant non-small cell lung cancer (NSCLC)
  作者：Yuchen Zhang、Lexian Tong、Fangjie Yan、Ping Huang、Cheng-Liang Zhu、Chenghao Pan

  DOI：10.1016/j.bioorg.2024.107394

  日期：2024.6

  treating non-small-cell lung cancer (NSCLC). However, there are no approved inhibitors for the C797S resistance mutation caused by the third-generation EGFR inhibitor (Osimertinib). Therefore, the development of fourth-generation EGFR inhibitors is urgent. In this study, we clarified the structure–activity relationship of several synthesized compounds as fourth-generation inhibitors against human triple

  表皮生长因子受体（EGFR）是治疗非小细胞肺癌（NSCLC）研究最多的药物靶点之一。然而，针对第三代EGFR抑制剂（奥希替尼）引起的C797S耐药突变，目前尚无批准的抑制剂。因此，开发第四代EGFR抑制剂刻不容缓。在这项研究中，我们阐明了几种合成化合物作为人类三重（Del19/T790M/C797S）突变第四代抑制剂的结构-活性关系。代表性化合物对 EGFR 显示出有效的抑制活性，IC 值为 0.55 nM，并显着抑制含有 EGFR 的 Ba/F3 细胞系的增殖，IC 值为 43.28 nM。此外，还表现出良好的药代动力学特性和优异的功效。总体而言，该化合物可以被认为是克服 EGFR C797S 介导的突变的有希望的候选者。
• 稠环-2-氨基嘧啶类化合物及其组合物和用途
  申请人：浙江大学智能创新药物研究院

  公开号：CN116082399A

  公开（公告）日：2023-05-09

  本发明公开了一种稠环‑2‑氨基嘧啶类化合物及其组合物和用途，具有式I所示的结构，或者其立体异构体、药学上可接受的盐，其中Y、Z、W各自选自C或N；X选自Cl、CF3。R1选自缺失、H、C1‑4烷烃基、含1‑2个杂原子的7‑11元螺环基、含1‑2个杂原子的4‑6元杂环基，其中杂原子为氮、氧中的至少一种；R2选自缺失、甲基、三氟甲基、C1‑4烷烃基；R3选自缺失、H、甲基、异丙基、C1‑4烷烃基。本发明化合物对EGFRL858R/T790M/C797S突变的细胞增殖性疾病有着良好的治疗效果并且对于野生型EGFR有着良好的选择性，同时本发明化合物具备可口服的潜质且有较好的安全性。
• PAGLIETTI G.; BOIDO V.; SPARATORE F., FARMACO, ED. SCI. <FRPS-AX>, 1975, 30, NO 6, 505-511
  作者：PAGLIETTI G.、 BOIDO V.、 SPARATORE F.

  DOI：——

  日期：——
• US7919510B2
  申请人：——

  公开号：US7919510B2

  公开（公告）日：2011-04-05