Mathé-Allainmat M, Le Gall M, Jellimann C, Andrieux J, Langlois M
CNRS-BIOCIS (UPRES A 8076), Université de Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.
Bioorg Med Chem. 1999 Dec;7(12):2945-52. doi: 10.1016/s0968-0896(99)00236-9.
Naphthalene melatoninergic ligands with alkyl groups (Me, Et, Pr, Bz) in the beta position of the ethylamido chain were synthesised. The affinity of the compounds for chicken brain melatonin receptors was evaluated using 2-[125I]-iodomelatonin as the radioligand. An increase in the affinity was observed with the beta-methyl derivatives and the greatest increase was seen with the (-) enantiomers. The introduction of a 2- or 7-MeO group on the naphthalene ring and the lengthening (Et, Pr) of the alkylamido chain gave potent compounds such as (-)1h (Ki = 24 pM). The functional activity of these compounds was evaluated by the aggregation of melanophores in Xenopus laevis tadpoles. The potency to produce lightening of the skin of Xenopus laevis was related to the affinities values of the molecules at melatonin chicken brain receptors. The most potent ligands were found to be full agonists and compound 1h was 25 fold more potent than melatonin in this bioassay.
合成了在乙酰胺链的β位带有烷基（甲基、乙基、丙基、苄基）的萘褪黑素能配体。以2-[¹²⁵I] -碘褪黑素作为放射性配体，评估了这些化合物对鸡脑褪黑素受体的亲和力。观察到β-甲基衍生物的亲和力增加，且（-）对映体的增加最为显著。在萘环上引入2-或7-甲氧基以及延长烷基酰胺链（乙基、丙基）得到了强效化合物，如（-）1h（Ki = 24 pM）。通过非洲爪蟾蝌蚪黑素细胞的聚集来评估这些化合物的功能活性。使非洲爪蟾皮肤变浅的效力与分子在鸡脑褪黑素受体上的亲和力值相关。发现最有效的配体是完全激动剂，在该生物测定中化合物1h的效力比褪黑素高25倍。
