BETA-SUBSTITUTED BETA-AMINO ACIDS AND ANALOGS AS CHEMOTHERAPEUTIC AGENTS

摘要

&bgr;-Substituted &bgr;-amino acids, &bgr;-substituted &bgr;-amino acid derivatives, and &bgr;-substituted &bgr;-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The &bgr;-substituted &bgr;-amino acid derivatives and &bgr;-substituted &bgr;-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the &bgr;-substituted &bgr;-amino acid derivatives and &bgr;-substituted &bgr;-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The &bgr;-substituted &bgr;-amino acid derivatives and &bgr;-substituted &bgr;-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The &bgr;-substituted &bgr;-amino acid derivatives and &bgr;-substituted &bgr;-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.