Synthesis and structure-activity relationships of novel dipeptides and reduced dipeptides as ligands for melanocortin subtype-4 receptor.

Abstract

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.

• Authors: Qing Shi, Paul L Ornstein, Karin Briner, Timothy I Richardson, Macklin B Arnold, Ryan T Backer, Jennifer L Buckmaster, Emily J Canada, Christopher W Doecke, Larry W Hertel, Nick Honigschmidt, Hansen M Hsiung, Saba Husain, Steve L Kuklish, Michael J Martinelli, Jeffrey T Mullaney, Thomas P O'Brien, Matt R Reinhard, Roger Rothhaar, Jikesh Shah, Zhipei Wu, Chaoyu Xie, John M Zgombick, Matthew J Fisher
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 9 Pg. 2341-6 (May 01 2006) ISSN: 0960-894X [Print] England
• PMID: 16297618 (Publication Type: Journal Article)

Chemical References

• Dipeptides
• Ligands
• Piperazines
• Receptor, Melanocortin, Type 4

Topics

• Dipeptides (chemical synthesis, chemistry, pharmacology)
• Ligands
• Molecular Structure
• Piperazines (chemistry)
• Protein Binding
• Receptor, Melanocortin, Type 4 (chemistry, drug effects)
• Stereoisomerism
• Structure-Activity Relationship