TY - JOUR
T1 - Structure-activity relationships of melanocortin agonists containing the benzimidazole scaffold
AU - Todorovic, Aleksandar
AU - Joseph, Christine G.
AU - Sorensen, Nicholas B.
AU - Wood, Michael S.
AU - Haskell-Luevano, Carrie
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/5
Y1 - 2007/5
N2 - 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 nm to no stimulation at up to 100 μM 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.
AB - 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 nm to no stimulation at up to 100 μM 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.
KW - Benzimidazole
KW - Melanocortin
KW - Obesity
KW - Solid-phase
KW - Synthesis
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U2 - 10.1111/j.1747-0285.2007.00511.x
DO - 10.1111/j.1747-0285.2007.00511.x
M3 - Article
C2 - 17539826
AN - SCOPUS:34249309635
SN - 1747-0277
VL - 69
SP - 338
EP - 349
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
IS - 5
ER -