title: Synthesis and in vitro antitumor activities of novel benzyl urea analogues of sorafenib.
abstract: A novel series of benzyl urea analogues based on the structural modification of sorafenib were synthesized. Their in vitro antitumor activities against MX-1, HepG2, Ketr3 and HT-29 were evaluated using the standard MTT assay. While several target compounds showed inhibitory activity against multiple cancer cell lines, compound 9 was of particular interest, demonstrating IC50 values (5.69-13.6 micromol x L(-1)) comparable to those of sorafenib. Furthermore, compounds 20 and 23 showed more potent inhibitory activity against HT-29 and MX-1 when compared to sorafenib. In particular, compound 20 bearing the N-3-pyridyl moiety not only exhibited greater inhibitory activity against HT-29 cell line (IC50 3.82 micromol x L(-1)), but also had improved solubility at pH 7.2, is worthy of further investigation as a lead to identify novel antitumor agents.
authors.affiliation: Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: Chen-Shu
authors.initials: CS
authors.lastname: Lu
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: Da-Li
authors.initials: DL
authors.lastname: Yin
authors.forename: Chen
authors.initials: C
authors.lastname: Ma
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Chen
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D000077157:Sorafenib; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D014508:Urea; D000077157:Sorafenib