4-(3',4'-dichlorophenyl)amino-6-nitroquinazoline | 691369-18-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-(3',4'-dichlorophenyl)amino-6-nitroquinazoline
• 英文别名: N-(3,4-dichlorophenyl)-6-nitroquinazolin-4-amine；4-(3,4-dichlorophenylamino)-6-nitroquinazoline
• CAS: 691369-18-3
• 化学式: C₁₄H₈Cl₂N₄O₂
• 分子量: 335.149
• InChiKey: SXUYOGVJZUSXKB-UHFFFAOYSA-N

物化性质

• 沸点：
  502.0±50.0 °C(Predicted)
• 密度：
  1.582±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3',4'-dichlorophenyl)amino-6-nitroquinazoline 在 tin(ll) chloride 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以86%的产率得到N4-(3,4-dichlorophenyl)quinazoline-4,6-diamine
  参考文献：
  名称：

  旨在发现突变型EGFR抑制剂；有效的4-芳基氨基-6-脲基和硫脲基-喹唑啉衍生物的设计，合成及体外生物学评价

  摘要：

  设计，合成和评价了具有C-6脲基和硫脲基侧链以及在C-4苯胺基部分具有各种取代基的一系列新的4-苯胺基喹唑啉，并将其评估为野生型（WT）和突变型EGFR抑制剂。大多数化合物抑制EGFR激酶野生型（EGFR WT）的IC 50值都在低纳摩尔范围（<0.495–9.05 nM），并且比参考化合物吉非替尼在表达BaF / 3的EGFR WT中显示出更强的细胞毒性作用。测定了所有合成化合物对吉非替尼不敏感的双突变体表达Del19 / T790M的Ba / F3和表达Ba / F3的L858R / T790M的抗增殖作用。化合物4d，6f，7e表现出显着的抑制作用（IC 50 与拉帕替尼（60.1 nM）相比 ，这些突变株中的Hs2 = 1.76–2.38μM，并且具有显着的Her2酶抑制（IC 50 = 19.2–40.6 nM）。证明了化合物6d，6f，7a，7b和8b的结合模式。此外，测试了对

  DOI：

  10.1016/j.bmc.2016.05.063
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 溶剂黄146 作用下， 反应 17.0h， 生成 4-(3',4'-dichlorophenyl)amino-6-nitroquinazoline
  参考文献：
  名称：

  Design, Synthesis and Biological Evaluation of Novel Quinazoline-Based Anti-inflammatory Agents Acting as PDE4B Inhibitors

  摘要：

  设计、合成并筛选了一系列基于喹唑啉的化合物（IIIa–d、VIa–f、IXa–f），以评估它们对PDE4B亚型的抑制活性。评估了目标化合物（IIIa–d、VIa–f、IXa–f）的体内抗炎作用及其对肿瘤坏死因子（TNF-α）水平的影响。在所有合成的化合物中，IXb、IXd和IXf对PDE4B酶表现出良好的抑制活性，抑制百分比分别为42％、62％和68％。与吲哚美辛相比，大多数测试化合物显示出强大的抗炎活性，TNF-α水平显著降低。还检查了测试化合物的致溃疡作用。测试动物在接受命中化合物的口服给药后，胃粘膜保持完整。此外，对接研究用于探索活性化合物在PDE4B酶上的可能结合模式，并说明活性命中对PDE4B亚型的选择性。

  DOI：

  10.1248/cpb.c14-00737

文献信息

• Design, Synthesis and Biological Evaluation of Novel Quinazoline-Based Anti-inflammatory Agents Acting as PDE4B Inhibitors
  作者：Rabah Ahmed Taha Serya、Abeer Hussin Abbas、Nasser Saad Mohamed Ismail、Ahmed Esmat、Dalal Abdelrahman Abou El Ella

  DOI：10.1248/cpb.c14-00737

  日期：——

  A novel series of quinzoline based compounds (IIIa–d, VIa–f, IXa–f) were designed, synthesized and screened for their inhibitory activity towards the PDE4B isoform. The in vivo anti-inflammatory effect of the titled compounds (IIIa–d, VIa–f, IXa–f) as well as their effect on the level of tumor necrosis factor (TNF-α) were evaluated. Among all of the synthesized compounds, IXb, IXd and IXf, exhibited good inhibitory activity against PDE4B enzyme with inhibition percentages of 42, 62 and 68%, respectively. Most of the tested compounds showed potent anti-inflammatory activity compared to indomethacin with a marked decrease in TNF-α level. The ulcerogenic effect of the tested compounds was also examined. The gastric mucosa of the tested animals remained intact after oral administration of the hit compounds. Additionally, docking study was used to explore the possible binding mode of the active compounds on the PDE4B enzyme as well as to illustrate the selectivity of the active hits on the PDE4B isoform.

  设计、合成并筛选了一系列基于喹唑啉的化合物（IIIa–d、VIa–f、IXa–f），以评估它们对PDE4B亚型的抑制活性。评估了目标化合物（IIIa–d、VIa–f、IXa–f）的体内抗炎作用及其对肿瘤坏死因子（TNF-α）水平的影响。在所有合成的化合物中，IXb、IXd和IXf对PDE4B酶表现出良好的抑制活性，抑制百分比分别为42％、62％和68％。与吲哚美辛相比，大多数测试化合物显示出强大的抗炎活性，TNF-α水平显著降低。还检查了测试化合物的致溃疡作用。测试动物在接受命中化合物的口服给药后，胃粘膜保持完整。此外，对接研究用于探索活性化合物在PDE4B酶上的可能结合模式，并说明活性命中对PDE4B亚型的选择性。
• Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates
  作者：Bhavin Marvania、Pei-Chih Lee、Ravi Chaniyara、Huajin Dong、Sharda Suman、Rajesh Kakadiya、Ting-Chao Chou、Te-Chang Lee、Anamik Shah、Tsann-Long Su

  DOI：10.1016/j.bmc.2011.01.055

  日期：2011.3

  A series of N-mustard-quinazoline conjugates was synthesized and subjected to antitumor studies. The N-mustard pharmacophore was attached at the C-6 of the 4-anilinoquinazolines via a urea linker. To study the structure-activity relationships of these conjugates, various substituents were introduced to the C-4 anilino moiety. The preliminary antitumor studies revealed that these agents exhibited significant antitumor activity in inhibiting various human tumor cell growths in vitro. Compounds 21b, 21g, and 21h were selected for further antitumor activity evaluation against human breast carcinoma MX-1 and prostate PC-3 xenograft in animal model. These agents showed 54-75% tumor suppression with low toxicity (5-7% body-weight changes). We also demonstrate that the newly synthesized compounds are able to induce DNA cross-linking through alkaline agarose gel shift assay and inhibited cell cycle arrest at G2/M phase. (C) 2011 Elsevier Ltd. All rights reserved.
• 4-Arylamino-6-nitroquinazolines: Synthesis and their activities against neglected disease leishmaniasis
  作者：Syed Muhammad Saad、Nida Ghouri、Shahnaz Perveen、Khalid Mohammed Khan、M. Iqbal Choudhary

  DOI：10.1016/j.ejmech.2015.11.016

  日期：2016.1

  4-Arylamino-6-nitroquinazolines (2-25) were synthesized and evaluated for their leishmanicidal activities against Leishmania major promastigotes in vitro with IC50 values = 1.87-61.48 mu M. Among the twenty four synthetic derivatives, 4-[4'-(methylsulfanyl)phenyljamino-6-nitroquinazoline (21), and 4-(2'-methoxyphenyl)amino-6-nitroquinazoline (8) showed excellent antileishmanial activities with IC50 values 1.87 +/- 0.31 and 437 +/- 0.02 mu M, respectively, more active than the standard drug, pentamidine (IC50 = 5.09 +/- 0.09 mu M). Compound 16 (IC50 = 6.53 +/- 0.21 mu M) displayed an activity comparable to the standard. Compounds 15 (IC50 = 9.04 +/- 0.03 mu M), 18 (IC50 = 12.28 +/- 0.18 mu M),14 (IC50 = 19.87 +/- 0.22 mu M), and 5 (IC50 = 24.03 +/- 2.71 mu M) also showed good activities. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Toward discovery of mutant EGFR inhibitors; Design, synthesis and in vitro biological evaluation of potent 4-arylamino-6-ureido and thioureido-quinazoline derivatives
  作者：Samar Mowafy、A. Galanis、Zainab M. Doctor、Raymond M. Paranal、Deena S. Lasheen、Nahla A. Farag、Pasi A. Jänne、Khaled A.M. Abouzid

  DOI：10.1016/j.bmc.2016.05.063

  日期：2016.8

  evaluated as wild type (WT) and mutant EGFR inhibitors. Most of the compounds inhibited EGFR kinase wild type (EGFR WT) with IC50 values in the low nanomolar range (<0.495–9.05 nM) and displayed more potent cytotoxic effect in BaF/3 expressing EGFR WT than reference compound gefitinib. The anti-proliferative effect of all synthesized compounds against gefitinib insensitive double mutant cell lines Ba/F3

  设计，合成和评价了具有C-6脲基和硫脲基侧链以及在C-4苯胺基部分具有各种取代基的一系列新的4-苯胺基喹唑啉，并将其评估为野生型（WT）和突变型EGFR抑制剂。大多数化合物抑制EGFR激酶野生型（EGFR WT）的IC 50值都在低纳摩尔范围（<0.495–9.05 nM），并且比参考化合物吉非替尼在表达BaF / 3的EGFR WT中显示出更强的细胞毒性作用。测定了所有合成化合物对吉非替尼不敏感的双突变体表达Del19 / T790M的Ba / F3和表达Ba / F3的L858R / T790M的抗增殖作用。化合物4d，6f，7e表现出显着的抑制作用（IC 50 与拉帕替尼（60.1 nM）相比 ，这些突变株中的Hs2 = 1.76–2.38μM，并且具有显着的Her2酶抑制（IC 50 = 19.2–40.6 nM）。证明了化合物6d，6f，7a，7b和8b的结合模式。此外，测试了对