多靶点酪氨酸激酶抑制剂阿法替尼及其类似物的研究进展

刘丹,栾天,袁莹,张磊

中国药学杂志 ›› 2014, Vol. 49 ›› Issue (24) : 2145-2149.

PDF(1894 KB)
PDF(1894 KB)
中国药学杂志 ›› 2014, Vol. 49 ›› Issue (24) : 2145-2149. DOI: 10.11669/cpj.2014.24.001
综述

多靶点酪氨酸激酶抑制剂阿法替尼及其类似物的研究进展

  • 刘丹,栾天,袁莹,张磊
作者信息 +

Advance in Research for Afatinib and Its Analogues, the Multi-Target Tyrosine Kinase Inhibitor

  • LIU Dan, LUAN Tian, YUAN Ying, ZHANG Lei
Author information +
文章历史 +

摘要

目的 综述多靶点酪氨酸激酶抑制剂阿法替尼及其类似物的最新研究进展。方法 通过查阅国内外相关文献,分别归纳了阿法替尼的合成方法、阿法替尼类似物的设计与合成及其抗肿瘤活性、阿法替尼的抗肿瘤活性与构效关系及其药动学与不良反应。结果 对阿法替尼及其类似物的研究进展进行了比较全面的总结。结论 尽管阿法替尼的不良反应较多,但其仍具有良好的发展前景,阿法替尼类似物值得进一步研究。

Abstract

OBJECTIVE To review the lastest research progress afatinib and its analogues, which are multi-target tyrosine kinase inhibitor. METHODS By consulting references, the synthesis afatinib, the design, synthesis and antitumor activity its analogues are summarized. the antitumor activity, structure-activity relationship, pharmacokinetic research, adverse reaction are also summarized. RESULTS The research progress afatinib and its analogues was comprehensively summarized. CONCLUSION Although afatinib has much adverse reaction, it still has a good prospect and its analogues may be worth further studying.

关键词

阿法替尼 / 喹唑啉衍生物 / 酪氨酸激酶抑制剂

Key words

afatinib / quinazoline analogue / tyrosine kinase inhibitor

引用本文

导出引用
刘丹,栾天,袁莹,张磊. 多靶点酪氨酸激酶抑制剂阿法替尼及其类似物的研究进展[J]. 中国药学杂志, 2014, 49(24): 2145-2149 https://doi.org/10.11669/cpj.2014.24.001
LIU Dan, LUAN Tian, YUAN Ying, ZHANG Lei. Advance in Research for Afatinib and Its Analogues, the Multi-Target Tyrosine Kinase Inhibitor[J]. Chinese Pharmaceutical Journal, 2014, 49(24): 2145-2149 https://doi.org/10.11669/cpj.2014.24.001
中图分类号: R944   

参考文献

[1] CARMI C, MOR M, PETRONINI P G, et al. Clinical perspectives for irreversible tyrosine kinase inhibitors in cancer. Biochem Pharmacol, 2012, 84(11):1388-1399. [2] Boehringer Ingelheim Pharma. Quinazoline derivatives, medicaments containing said compounds, their utilization and method for the production thereof: Germany, WO 0250043A1. 2002-06-27. [3] Boehringer Ingelheim Pharma. Utilization inhibitors EGFR-mediated signal transduction for the treatment benign prostatic hyperplasia (BPH)/prostatic hypertrophy: Germany, WO03094921A2. 2003-11-20. [4] XU X N. The preparation Afatinib: China, 201310173504. 9. 2013-8-21. [5] XU X N. The preparation Afatinib: China, 201310180796. 9 . 2013-9-11. [6] XU X N. The preparation the intermediate 4-chloro-6-amino-7-hydroxy quinazoline: China, 201310181198. 3. 2013-9-11. [7] XU X N. The preparation Afatinib: China, 201310182778. 4. 2013-8-14. [8] ZHANG X, PENG T, JI X, et al. Design, synthesis and biological evaluation novel 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors the epidermal growth factor receptor. Bioorg Med Chem, 2013, 21(24):7988-7998. [9] JI X, PENG T, ZHANG X, et al. Design, synthesis and biological evaluation novel 6-alkenylamides substituted 4-anilinothieno pyrimidines as irreversible epidermal growth factor receptor inhibitors. Bioorg Med Chem, 22(7): 2014, 22(7): 2366-2378. XU Q Y, MOU H B, XU N. Mechanism and treatment associated with resistance to EGFR-TKI. J Int Oncol(国际肿瘤学杂志), 2012, 39(5):355-359. SOLCA F, DAHL G, ZOEPHEL A, et al. Target binding properties and cellular activity afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther, 2012, 343(2):342-350. CHEN X, ZHU Q, ZHU L, et al. Clinical perspective afatinib in non-small cell lung cancer . Lung Cancer, 2013, 81(2): 155-161. LI J, WU X H, LIU Z B, et al. Overcoming acquired resistance to gefitinib in NSCLC with EGFR T790M mutation using combination afatinib and cetuximab. Tumor(肿瘤), 2013, 33(7): 619-623. DIENSTMANN R, DOSSO S D, FELIP E, et al. Drug development to overcome resistance to EGFR inhibitors in lung and colorectal cancer. Mol Oncol, 2012, 6(1):15-26. MORAN C. Importance molecular features non-small cell lung cancer for choice treatment. Am J Pathol, 2011, 178(5):1940-1948. ROSKOSKI R JR. The ErbB/HER family protein-tyrosine kinases and cancer . Pharmacol Res, 2014, 20(79):34-74. WANG Y,LONG Y Q. Advances in small-molecule inhibitors protein tyrosine kinases. Chin J Org Chem(有机化学), 2011, 31(10):1595-1606. WARD R A, ANDERTON M J, ASHTON S, et al. Structure and Reactivity-Based development covalent inhibitors the activating and gatekeeper mutant forms the epidermal growth factor receptor (EGFR). J Med Chem, 2013,56(17):7025-7048. ROSKOSKI R JR. ERK1/2 MAP kinases: Structure, function, and regulation. Pharmacol Res, 2012, 66(2): 105-143. CHANG S, ZHANG L, XU S, et al. Design, synthesis, and biological evaluation novel conformationally constrained inhibitors targeting epidermal growth factor receptor threonine790→methionine790 mutant . J Med Chem, 2012, 55(6): 2711-2723. HOELDER S, CLARKE P A, WORKMAN P. Discovery small molecule cancer drugs: Successes, challenges and opportunities . Mol Oncol, 2012, 6(2):155-176. GIROUX S. Overcoming acquired resistance to kinase inhibition: The cases EGFR, ALK and BRAF. Bioorg Med Chem Lett, 2013, 23(2):394-401. CHEN X, DU Y, SUN H, et al. Synthesis and biological evaluation novel tricyclic oxazine and oxazepine fused quinazolines. Part 1: Erlotinib analogs. Bioorg Med Chem Lett, 2014, 24(3):884-887. VACONDIO F, CARMI C, GALVANI E, et al. Long-lasting inhibition EGFR autophosphorylation in A549 tumor cells by intracellular accumulation non-covalent inhibitors. Bioorg Med Chem Lett, 2013, 23(19):5290-5294. HAN C, HUANG Z, ZHENG C, et al. Novel hybrids (Phenylsulfonyl)furoxan and anilinopyrimidine as potent and selective epidermal growth factor receptor inhibitors for intervention Non-Small-Cell lung cancer. J Med Chem, 2013(56): 4738-4748. WANG Y F,SONG Y. Progress in the therapy afatinib for non-small cell lung cancer. Chin J Lung Dis(Elec Edit)(中华肺部疾病杂志电子版), 2012, 5(4):55-60. LI C L. Afatinib. Chin J Med Chem(中国药物化学杂志),2014, 24(1):82. PENG Y, SHIAO H, TU C,et al. Protein kinase inhibitor design by targeting the Asp-Phe-Gly (DFG) motif: The role the DFG motif in the design epidermal growth factor receptor inhibitors. J Med Chem, 2013, 56(10): 3889-3903.

基金

辽宁省教育厅科学研究一般项目(L2013171)
PDF(1894 KB)

Accesses

Citation

Detail

段落导航
相关文章

/