Melanoma is the most aggressive form of skin cancer and is the fastest growing type of cancer in the United States. We report here the synthesis of a novel series of quinazolinylmethoxybenzene derivatives 1a-c and their antiproliferative activities against A375 human melanoma cell line. Among them, urea compound 1a ($IC_{50};=;4.8;{mu}M$) having 4-chloro-3-trifluoromethylphenyl moiety showed superior antiproliferative activity to Sorafenib ($IC_{50};=;5.5;{mu}M$) as a reference compound. These results will helpful for designing structure of a therapeutic agent for the treatment of melanoma.