From Lab to Target: Pyrazole, Pyrazoline and Fused Pyrazole Derivatives as Receptor Tyrosine Kinase Inhibitors in Cancer Therapy

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Michael M. Sawiris, Omneya M. Khalil, Peter A. Halim, Marwa S. A. Hassan
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Abstract

Pyrazole derivatives have emerged as versatile scaffolds in the development of receptor tyrosine kinase inhibitors, offering promising avenues for targeted cancer therapy. Their therapeutic potential in cancer therapy is notable in many FDA-approved anticancer drugs. This review provides a comprehensive overview of the latest research from 2021 regarding novel pyrazole, pyrazoline, and fused pyrazole derivatives targeting receptor tyrosine kinases, namely: AXL, DDR, EGFR, FGFR, MET, CSF1R, RET, and VEGFR-2. This study focuses on the most active and promising candidates within each series of compounds. Key aspects covered include their cytotoxicity and enzyme inhibition results, with comparisons to reference drugs. The review also covers the molecular docking studies, highlighting critical binding interactions between the compounds and the protein kinase residues, and unveiling their molecular mechanisms of action. Structure–activity relationship analyses are also discussed, revealing the influence of structural modifications on biological activities. Furthermore, synthetic pathways for each series or key compounds are presented, offering a practical guide for researchers in the field. By integrating these elements, this review provides a solid foundation and rationale for the design, synthesis, and optimization of new pyrazole-based anticancer agents targeting receptor tyrosine kinases.

从实验室到靶点:吡唑、吡唑啉和融合吡唑衍生物作为受体酪氨酸激酶抑制剂在癌症治疗中的应用
吡唑衍生物已成为受体酪氨酸激酶抑制剂开发中的多功能支架,为靶向癌症治疗提供了有希望的途径。在许多fda批准的抗癌药物中,它们在癌症治疗中的治疗潜力是显著的。本文综述了2021年以来针对酪氨酸受体激酶的新型吡唑、吡唑啉和融合吡唑衍生物的最新研究,即:AXL、DDR、EGFR、FGFR、MET、CSF1R、RET和VEGFR-2。本研究的重点是在每个系列化合物中最具活性和最有前途的候选化合物。所涵盖的关键方面包括它们的细胞毒性和酶抑制结果,并与参考药物进行比较。综述还涵盖了分子对接研究,重点介绍了化合物与蛋白激酶残基之间的关键结合相互作用,并揭示了它们的分子作用机制。并讨论了构效关系分析,揭示了结构修饰对生物活性的影响。此外,还介绍了每个系列或关键化合物的合成途径,为该领域的研究人员提供了实用的指导。通过整合这些元素,本文综述为设计、合成和优化靶向受体酪氨酸激酶的新型吡唑类抗癌药物提供了坚实的基础和理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
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