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Towards the Development of Mixed MT 1 ‐Agonist/MT 2 ‐Antagonist Melatonin Receptor Ligands
Author(s) -
Spadoni Gilberto,
Bedini Annalida,
Guidi Tomaso,
Tarzia Giorgio,
Lucini Valeria,
Pannacci Marilou,
Fraschini Franco
Publication year - 2006
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200600133
Subject(s) - melatonin , melatonin receptor , agonist , receptor , antagonist , chemistry , ligand (biochemistry) , in vitro , derivative (finance) , partial agonist , stereochemistry , pharmacology , biochemistry , endocrinology , biology , financial economics , economics
Herein we report attempts to optimize the pharmacological properties of 5‐(2‐hydroxyethoxy)‐ N ‐acetyltryptamine (5‐HEAT), a melatonin receptor ligand previously described by us. Several 5‐substituted and 2,5‐disubstituted N ‐acyltryptamines were synthesized and evaluated in vitro for the human cloned MT 1 and MT 2 receptors. From this series of N ‐acyltryptamines the 2‐bromo derivative ( 5 c ) retains the interesting efficacy profile of 5‐HEAT and shows increased melatonin receptor affinities; it represents one of the first examples of a high‐affinity MT 1 agonist/MT 2 antagonist. Some other full agonists for both melatonin receptors which exhibit similar or increased affinity relative to that of melatonin were obtained.