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Structure–Activity Relationships of Melanocortin Agonists Containing the Benzimidazole Scaffold
Author(s) -
Todorovic Aleksandar,
Joseph Christine G.,
Sorensen Nicholas B.,
Wood Michael S.,
HaskellLuevano Carrie
Publication year - 2007
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00511.x
Subject(s) - melanocortin , benzimidazole , melanocortin 3 receptor , melanocortin receptor , agonist , receptor , melanocortin 4 receptor , chemistry , partial agonist , energy homeostasis , g protein coupled receptor , biochemistry , pharmacology , biology , endocrinology , organic chemistry
The melanocortin system has been implicated in regulating various physiological processes including pigmentation, energy homeostasis, obesity, steroidogenesis cardiovascular, and exocrine gland function. The five melanocortin receptors that belong to the super family of G protein‐coupled receptors are stimulated by naturally occurring agonists. The aim of this research was focused on the design, synthesis, and pharmacological characterization of melanocortin ligands that contain the 1,2,5‐trisubstituted benzimidazole scaffold. A series of benzimidazole analogues, with three points of diversity at positions 1, 2, and 5, were designed, synthesized, pharmacologically assayed at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R and resulted in ligands possessing a range of agonist activity from n m to no stimulation at up to 100 μ M concentrations. This study demonstrates that the benzimidazole structure template can be appended with key melanocortin agonist amino acids for the design melanocortin receptor agonist ligands.