Design and optimization of orally spleen tyrosine kinase (SYK) inhibitors for treatment of solid tumor.
作者： Cheng Wang , Xin Wang , Yao Li , Tianqi Wang , Zhi Huang
DOI: 10.1016/J.BIOORG.2019.103547
关键词:
摘要: Abstract As the aim to discover orally SYK inhibitors for solid tumor treatment, a series of novel derivatives based on imidazo[1,2-a]pyrazine scaffold were designed, synthesized and evaluated. Structure-activity relationship study both enzymatic cellular assays led identification compound 12f. The inhibitor 12f showed potent antitumor activity against tumors with favorable drug-like properties lipophilicity solubility. could induce cell apoptosis ovarian lung cancer lines. In SKOV3 xenograft mouse model, oral administration significant tumour regression without obvious toxicity. improved limited response traditional in vitro vivo. Taken together, this may act as promising lead further development new therapy.
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