59067-29-7Relevant academic research and scientific papers
Modular synthesis of non-peptidic bivalent NPY Y1 receptor antagonists
Weiss, Stefan,Keller, Max,Bernhardt, Guenther,Buschauer, Armin,Koenig, Burkhard
experimental part, p. 9858 - 9866 (2009/04/06)
According to a 'bivalent ligand approach' to increase the affinity of the potent argininamide-type NPY Y1 receptor antagonist BIBP-3226, dimeric ligands were synthesized in which two molecules of the parent compound were linked by different spacers via NG-acylation at the guanidino groups. A synthetic route for the preparation of the title compounds was developed, which includes a copper(I)-catalyzed azide alkyne cycloaddition as the key step. Three bivalent analogues of BIBP-3226 were prepared showing nanomolar antagonistic activity and binding affinity to the NPY Y1 receptor (calcium assay on HEL cells, radioligand binding assay on SK-N-MC cells), but these ligands were not superior to the parent compound and there was no correlation with the length or the chemical nature of the spacer. A trivalent BIBP-3226 derivate showed, surprisingly, no affinity to the NPY Y1 receptor at all.
