Synthesis of new arylalkoxy amido derivatives as melatoninergic ligands.
Bioorg Med Chem
; 11(5): 789-800, 2003 Mar 06.
Article
em En
| MEDLINE
| ID: mdl-12538010
ABSTRACT
Amido derivatives 10-18 of the corresponding oxyamines were synthesised as melatoninergic ligands by the reaction of hydroxyphtalimide with the halogeno derivatives or the corresponding alcohols using Mitsunobu reaction conditions. The affinity of the compounds for chicken brain melatonin receptors and recombinant human MT(1) and MT(2) receptors was evaluated using 2-[125I]-iodomelatonin as the radioligand. Overall, the introduction of an oxygen atom in the amido chain was not a favourable parameter as the compounds were less potent than the corresponding deoxy derivatives. However, nanomolar compounds were obtained with the arylethyloxy derivatives (13c (R'=nPr), chicken brain, hMT(1), hMT(2), K(i) values 4.8, 3.86, 2.4 nM, respectively) and the 2,7-dimethoxynaphthalene derivatives (17c (R'=nPr), chicken brain, hMT(1), hMT(2), K(i) values 0.04, 0.13, 0.1 nM, respectively). The functional activity of these compounds was evaluated by the aggregation of melanophores in Xenopus laevis tadpoles and the potency was related to the affinity of the molecules for melatonin receptors. The compounds were found to be full agonists and compound 17a was 20-fold more potent than melatonin in this bioassay.
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Base de dados:
MEDLINE
Assunto principal:
Alcanos
/
Amidas
/
Melatonina
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
França