| The Peripheral Benzodiazepine Receptor (PBR) is located on the outer membrane of mitochondria, and has been found to be in higher density in cancer cells when compared to normal cells. The ligand of the Periferal Benzodiazepine Receptor, which is a specific molecular carrier ligand, could be used to carry the anticancer drug to the target organ. This should result in a higher bioaccumulation of the cytotoxic drug in the cancerous tissue and, as a consequence, reduced toxicity to normal cells. We choose platinum as the cytotoxic agent, since it is widely known that platinum complexes are used as chemotherapeutic agents covalently bound to the mitochondrial DNA in the N-7 position of guanine. The use of PBR ligand-platinum complexes (PBR-Pt) as target drugs is one of the alternatives to minimize the secondary effects and enhance selectivity on human cancer cells. In the present study, a ligand PBR---platinum complex (PBR-Pt) was synthesized by coupling 7-chloro-5-(1-methyl-2-imidazolyl)-1-methyl-1,4-benzo-diazepine-2-one with K2PtCl4 with a 62% yield. The key intermediate for this synthesis is 2-amino-5-chlorophenyl-2-(1-methylimidazolyl) ketone. This compound was prepared simply and efficiently in a "one-pot" reaction using 2-amino-5-chlorobenzoic acid and four equivalents of 1-methyl-2-lithiumimidazole. This method afforded the desired ketone in 92% yield. The target Benzodiazepine is obtained from the corresponding ketone in three steps in an overall yield of 70%. The spectroscopic data of the intermediates and the target compounds are included. The elemental analyses of these compounds are within the accepted difference of +/-0.4% showing evidence of the high purity obtained. |
