Synthesis of peripheral benzodiazepine receptor ligand as a molecular carrier of platinum and the PBR ligand-platinum complex as a potential anti-cancer agent

Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of mitochondria, and their density is increased in tumors. Thus, they may serve as an intracellular target. In the present study a PBR ligand-platinum complexes 5 and 6 were synthesized by coupling 7-chloro-1-methyl-5-pyridin-2-yl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (4) and (3) with K2PtCl4 in a 74% yield. The key intermediate for this synthesis is (2-amino-5-chlorophenyl) (pyridine-2-yl) methanone (1) and was prepared in a simple and efficient "one-pot" reaction using 2-amino-5-chlorobenzoic acid and four equivalents of pyridine-2-yllithium. This method afforded the desired ketone in an 82% yield. The target benzodiazepine 4 was obtained from ketone 1 in three steps in an overall yield of 74%. All the intermediates and the target compound were fully identified using spectroscopic techniques (1H-NMR, IR) and the elemental analyses are within the expected error of +/-0.4% and are evidence of the high purity obtained for each compound.