New potent biphalin analogues containing p-fluoro-L-phenylalanine at the 4,4′ positions and non-hydrazine linkers

Abstract

We report the synthesis and the biological evaluation of two new analogues of the potent dimeric opioid peptide biphalin. The performed modification is based on the replacement of two key structural elements of the native biphalin, namely: the hydrazine bridge which joins the two palindromic moieties and the phenylalanine residues at the 4,4′ positions of the backbone. The new analogues 9 and 10 contain 1,2-phenylenediamine and piperazine, respectively, in place of the hydrazidic linker and p-fluoro-L-phenylalanine residues at 4 and 4′ positions. Binding values are: Kiμ= 0: 51nM and Kiδ= 12: 8 nM for compound 9, Kiμ = 0: 09nM and Kiδ= 0: 11nM for analogue 10. © 2011 Springer-Verlag.