Discovery of substituted pyrazol-4-yl pyridazinone derivatives as novel c-Met kinase inhibitors

• Published in: Archives of pharmacal research Vol. 39; no. 4; pp. 453 - 464
• Main Authors: Kim, Eun-Young, Kang, Seung-Tae, Jung, Heejung, Park, Chi Hoon, Yun, Chang-Soo, Hwang, Jong Yeon, Byun, Byung Jin, Lee, Chong Ock, Kim, Hyoung Rae, Ha, Jae Du, Ryu, Do Hyun, Cho, Sung Yun
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.04.2016; 대한약학회
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Discovery; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Medicine; Pharmacology/Toxicology; Pharmacy; Proto-Oncogene Proteins c-met - antagonists & inhibitors; Pyridazines - chemical synthesis; Pyridazines - chemistry; Pyridazines - pharmacology; Research Article; 약학; Mesenchymal epithelial transition factor; Pyridazine derivatives; c-MET inhibitor; Kinase inhibitor
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-015-0703-7

A series of pyridazin-3-one substituted with morpholino-pyrimidine derivatives was synthesized and evaluated as tyrosine kinase inhibitors against c-Met enzyme, and anti-proliferative activities of Hs746T human gastric cancer cell line. Most of compounds exhibited good biological activity, while compound 10, 12a, 14a displayed excellent c-Met enzyme inhibitory activities and Hs746T cell-based activities.