Identification of novel N 1 -(2-aryl-1, 3-thiazolidin-4-one)-N 3 -aryl ureas showing potent multi-tyrosine kinase inhibitory activities

• Published in: European journal of medicinal chemistry 2018-02, Vol.146, p.368
• Main Authors: Qi, Baohui, Yang, Ying, He, Huan, Yue, Xupeng, Zhou, Yuting, Zhou, Xing, Chen, Yuying, Liu, Min, Zhang, Anmian, Wei, Fachang
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Models, Molecular; Molecular Structure; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Structure-Activity Relationship; Urea - analogs & derivatives; Urea - chemistry; Urea - pharmacology
• ISSN: 1768-3254
• DOI: 10.1016/j.ejmech.2018.01.061

A total of 29 novel compounds bearing N -(2-aryl-1, 3-thiazolidin-4-one)-N -aryl ureas were designed, synthesized and evaluated for their biological activities. The structure-activity relationships (SARs) and binding modes of this series of compounds were clarified together. Compound 29b was identified possessing high potency against multi-tyrosine kinases including Ron, c-Met, c-Kit, KDR, Src and IGF-1R, etc. In vitro antiproliferation and cytotoxicity of compound 29b against A549 cancer cell line were confirmed by IncuCyte live-cell imaging.