Synthesis and in vitro cytotoxicity of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 5; pp. 1169 - 1172
• Main Authors: CHERN, Jyh-Haur, SHIA, Kak-Shan, CHANG, Chung-Ming, LEE, Chung-Chi, LEE, Yen-Chun, TAI, Chia-Liang, LIN, Ying-Ting, CHANG, Chih-Shiang, TSENG, Huan-Yi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 08.03.2004
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - toxicity; Biological and medical sciences; Cell Line, Tumor; Fibroblasts - drug effects; General aspects; Humans; Imidazoles - chemical synthesis; Imidazoles - toxicity; Medical sciences; Pharmacology. Drug treatments; Pyrimidinones - chemical synthesis; Pyrimidinones - toxicity; Antineoplastic agent; Five membered ring; Nitrogen heterocycle; Toxicity; Cytotoxicity; In vitro; Pyridine derivatives; Cell line; Structure activity relation; Six membered ring; Chemical synthesis; Fibroblast; Tumor cell
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.12.073

A series of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives were synthesized and their anticancer cytotoxicity were evaluated in in vitro assay. It was found that the bulky aryl functionality in the 5-position of the 2-cyanoimino-4-imidazolidinone compounds was essential for the cytotoxicity of these heterocyclic compounds. Some of the derivatives exhibited modest cytotoxicity against a variety of cancer cell lines. One of the derivatives, [1-[6-(4-chlorophenoxy)hexyl]-5-oxo-4-phenyl-3-(4-pyridyl)tetrahydro-1H-2-imidazolyliden]aminomethanenitrile (Compound 11), exhibited the most potent cytotoxic activity with IC(50) in the nanomolar range. The cytotoxicity of these derivatives was selection with no apparent toxic effect toward normal fibroblasts.