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Towards the development of mixed MT(1)-agonist/MT(2)-antagonist melatonin receptor ligands
Gilberto Spadoni1, Annalida Bedini, Tomaso Guidi
1Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Urbino Carlo Bo, Piazza Rinascimento 6, Urbino, Italy.
Abstract:
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.
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