Add time:07/27/2019 Source:sciencedirect.com
Echinoderm microtubule-associated protein-like 4 (EML4)–anaplastic lymphoma kinase (ALK) is a valid therapeutic target for the treatment of EML4–ALK-positive non-small cell lung cancer (NSCLC). We discovered 12c as a novel and potent EML4–ALK inhibitor through structural optimization of 5a. In mice xenografted with 3T3 cells expressing EML4–ALK, oral administration of 12c demonstrated potent antitumor activity. This article describes the synthesis and biological evaluation of pyrazine-2-carboxamide derivatives along with studies of their structure–activity relationship (SAR) using computational modeling.
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