Synthesis and biological evaluation of new beta,beta'-disubstituted 6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl ethylamido melatoninergic ligands.
Tricyclic analogs of melatonin with alkyl and cycloalkyl moieties in the beta position of the ethylamido chain have been prepared and tested for their ability to activate pigment granule aggregation in Xenopus laevis melanophores. The introduction of two methyl groups in the beta position of the side-chain of the methoxyl-substituted ligands induces a synergistic effect in agonist potency, which, importantly, is maintained after the methoxyl substituent is removed. The presence of more bulky beta-substituents, regardless of the size of the R group, seems to lead to antagonism.
Tsotinis
A
A
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis-Zografou, 157 71 Athens, Greece. tsotinis@pharm.uoa.gr
Panoussopoulou
M
M
Hough
K
K
Sugden
D
D
D000818:Animals; D046508:Culture Techniques; D004347:Drug Interactions; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008547:Melanophores / Q000187:drug effects*; D008550:Melatonin / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D007211:Indoles; D008550:Melatonin