Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of the Epidermal Growth Factor Receptor Triple Mutant (EGFR L858R/T790M/C797S )

• Published in: Journal of medicinal chemistry Vol. 62; no. 15; pp. 7302 - 7308
• Main Authors: Shen, Jiayi, Zhang, Tao, Zhu, Su-Jie, Sun, Min, Tong, Linjiang, Lai, Mengzhen, Zhang, Rong, Xu, Wei, Wu, Ruibo, Ding, Jian, Yun, Cai-Hong, Xie, Hua, Lu, Xiaoyun, Ding, Ke
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 08.08.2019
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; LUNG-CANCER; EGFR INHIBITORS; GEFITINIB; RESISTANCE; OPTIMIZATION; MUTATIONS; DISCOVERY; AZD9291

Tertiary EGFRc797s mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFR(L858R/T790M/C797S) inhibitors. A...