Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8-nitroquinazolines as egfr signaling-targeted inhibitors
文献类型：期刊论文
| 作者 | Jin, Y; Li, HY; Lin, LP; Tan, JZ; Ding, J; Luo, XM; Long, YQ |
| 刊名 | Bioorganic & medicinal chemistry
 |
| 出版日期 | 2005-10-01 |
| 卷号 | 13期号:19页码:5613-5622 |
| 关键词 | Egfr inhibitor Quinazolines Erbb-2 Breast cancer Cellular signaling |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2005.05.045 |
| 通讯作者 | Long, yq() |
| 英文摘要 | The synthesis and biological activity of a series of novel 5-substituted-4-hydroxy-8-nitroquinazolines that may function as inhibitors of egfr- and/or erbb-2-related oncogenic signaling are described. these compounds were prepared by snar reaction of 5-chloro-4-hydroxy-8-nitroquinazo line with alkyl or aryl amines, or alkyl alcohol as nucleophiles. although the enzyme assay showed a weak inhibition effect against both egfr and erbb-2 tyrosine kinases, the cell-based antitumor activity turned out promising. compounds having 5-anilino substituent exhibit high potency with 5-(4-methoxy)anilino-4-hydroxy-8-nitroquinazoline (1h) being the best dual egfr/erbb-2 inhibitors, which effectively inhibited the growth of both egfr (mda-mb-468, ic50 < 0-01 mu m) and erbb-2 (sk-br-3, ic50 = 13 mu m) overexpressing human tumor cell lines in vitro. more interestingly, the variation of the substituent(s) at the 3- and/or 4-position of the 5-anilino portion was found to modulate the selectivity and potency dramatically. however, compounds having an alkylamino or alkyloxy group at the 5-position of 4-hydroxy-8-nitroquinazolines are essentially inactive. these results are consistent with molecular modeling observations. this study was the first attempt to identify new structural types of dual egfr/erbb-2-related signaling inhibitors by incorporation of the anilino group at the 5-position of 4-hydroxy-8-nitroquinazolines' core structure, providing promising new templates for further development of potent inhibitors targeting both egfr and erbb-2 tyrosine kinases. (c) 2005 elsevier ltd. all rights reserved. |
| WOS关键词 | GROWTH-FACTOR RECEPTOR ; TYROSINE KINASE INHIBITORS ; CANCER |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| WOS类目 | Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic |
| 语种 | 英语 |
| WOS记录号 | WOS:000231663300010 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2378298 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Long, YQ |
| 作者单位 | 1.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Shanghai Inst Mat Med,State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Drug Discovery & Design Ctr,Grad Sch, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jin, Y,Li, HY,Lin, LP,et al. Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8-nitroquinazolines as egfr signaling-targeted inhibitors[J]. Bioorganic & medicinal chemistry,2005,13(19):5613-5622. |
| APA | Jin, Y.,Li, HY.,Lin, LP.,Tan, JZ.,Ding, J.,...&Long, YQ.(2005).Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8-nitroquinazolines as egfr signaling-targeted inhibitors.Bioorganic & medicinal chemistry,13(19),5613-5622. |
| MLA | Jin, Y,et al."Synthesis and antitumor evaluation of novel 5-substituted-4-hydroxy-8-nitroquinazolines as egfr signaling-targeted inhibitors".Bioorganic & medicinal chemistry 13.19(2005):5613-5622. |
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来源：中国科学院大学
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