Design, synthesis and biological activity of N4-phenylsubstituted-7H-pyrrolo[2,3-d]pyrimidin-4-amines as dual inhibitors of aurora kinase A and epidermal growth factor receptor kinase.

作者: Sonali Kurup , Bradley McAllister , Pavlina Liskova , Trusha Mistry , Anthony Fanizza

DOI: 10.1080/14756366.2017.1376666

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摘要: Simultaneous inhibition of multiple kinases has been suggested to provide synergistic effects on tumour growth and resistance. This study describes the design, synthesis evaluation 18 compounds incorporating a pyrrolo[2,3-d]pyrimidine scaffold for dual epidermal factor receptor kinase (EGFR) aurora A (AURKA). Compounds 1-18 this demonstrate nanomolar EGFR micromolar AURKA. allow structure-activity relationships (SAR) analysis 4-anilino moiety AURKA inhibition. Compound 6, 4-methoxyphenylpyrrolo[2,3-d]pyrimidin-4-amine, demonstrates single-digit both provides evidence single molecule with activity against 2, most potent inhibitor from series, further evaluated in four different squamous cell head neck cancer lines downstream resulting

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