RESUMO
A series of benzylic piperazines (e.g., 4 and 5) attached to an 'address element', the dipeptide H-D-Tic-D-p-Cl-Phe-OH, 3 has been identified as ligands for the melanocortin subtype-4 receptor (MC4R). We describe herein the structure-activity relationship (SAR) studies on the N-terminal residue of the 'address element'. Several novel dipeptides and reduced dipeptides with high MC4R binding affinities and selectivity emerged from this SAR study.
Assuntos
Dipeptídeos/síntese química , Dipeptídeos/farmacologia , Receptor Tipo 4 de Melanocortina/efeitos dos fármacos , Dipeptídeos/química , Ligantes , Estrutura Molecular , Piperazinas/química , Ligação Proteica , Receptor Tipo 4 de Melanocortina/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Replacement of the aryl piperazine moiety in compound 1 with a variety of substituted benzylic piperazines (6) yields compounds that afford melanocortin receptor 4 (MCR4) activity. Analogs with ortho substitution on the aromatic ring afforded the highest affinity. Resolution of the stereocenter of the benzylic piperazine based privileged structure revealed that the R-enantiomer was more active.
