Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity.
Basic Information
ID: ALA4304751
Journal: ACS Med Chem Lett
Title: Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity.
Authors: Taniguchi T, Inagaki H, Baba D, Yasumatsu I, Toyota A, Kaneta Y, Kiga M, Iimura S, Odagiri T, Shibata Y, Ueda K, Seo M, Shimizu H, Imaoka T, Nakayama K.
Abstract: To obtain a new anticancer drug, we focused on FER tyrosine kinase. Starting with high-throughput screening with our in-house chemical library, compound 1, which has a pyridine moiety, was found. Referring to their X-ray crystal structure with FES proto-oncogene tyrosine kinase, as a surrogate of FER followed by chemical modification including scaffold hopping of the pyridine template, we discovered pyrido-pyridazinone derivatives with potent FER kinase inhibitory activity. Here, we disclose the structure-activity relationship on the scaffold and representative compound 21 (DS21360717), which showed in vivo antitumor efficacy in a subcutaneous tumor model.
CiteXplore: 31097992
DOI: 10.1021/acsmedchemlett.8b00631
Patent ID: ┄