Hybrid compounds as new Bcr/Abl inhibitors

A series of 2,4-disubstituted thiazole derivatives were designed and synthesized as new Bcr/Abl inhibitors by hybriding the structural moieties from FDA approved imatinib, nilotinib and dasatinib. The new inhibitors strongly suppressed the activity of Bcr/Abl kinase and potently inhibited the prolif...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2011-04, Vol.21 (7), p.1965-1968
Hauptverfasser:	Wang, Deping, Zhang, Zhang, Lu, Xiaoyun, Feng, Yubing, Luo, Kun, Gan, Jirong, Yingxue, Liu, Wan, Junting, Li, Xiang, Zhang, Fengxiang, Tu, Zhengchao, Cai, Qian, Ren, Xiaomei, Ding, Ke
Format:	Artikel
Sprache:	eng
Schlagworte:	2,4-Disubstituted thiazole Anticancer Antineoplastic agents Bcr/Abl kinase Biological and medical sciences cell growth Cell Line, Tumor Chronic myelogenous leukemia Drug Screening Assays, Antitumor enzyme inhibitors Fusion Proteins, bcr-abl - antagonists & inhibitors General aspects Humans Hybride compound leukemia Leukemia - pathology Medical sciences Models, Molecular Pharmacology. Drug treatments Structure-Activity Relationship Thiazoles - chemistry Thiazoles - pharmacology
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Zusammenfassung:	A series of 2,4-disubstituted thiazole derivatives were designed and synthesized as new Bcr/Abl inhibitors by hybriding the structural moieties from FDA approved imatinib, nilotinib and dasatinib. The new inhibitors strongly suppressed the activity of Bcr/Abl kinase and potently inhibited the proliferation of K562 and KU812 leukemia cancer cells. Compound 4i displayed comparable potency with that of nilotinib in both biochemical kinase assay and cancer cell growth inhibition assay. These inhibitors might serve as lead compounds for further developing new anticancer drugs.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2011.02.029