Synthesis of N1-phenethyl substituted indole derivatives as new melatoninergic agonists and antagonists.
The potency of new indolic N1-phenethyl substituted melatoninergic ligands with and without methyl groups in the alpha and beta position of the alkanamidoethyl side chain was examined using the pigment aggregation response in a clonal line of Xenopus laevis melanophores. The non 5-OMe substituted compounds, 8a--e, are all weak antagonists while introduction of the 5-OMe group, 9a--e, increases both agonist and antagonist activity except for 9c (R=C3H7), which is only an agonist and 9e (R=c-C4H7), which is only an antagonist. Introduction of an alpha-methyl group into the 5-OMe derivatives, 14a-e, reduces the agonist potency while introduction of a beta-methyl group has only a small effect on either the agonist or antagonist potency. Double beta-methyl substitution of the 5-OMe derivatives, 20a--e, generally increases the agonist potential (20c, R=C3H7 is the most potent agonist of the compounds described) and decreases the antagonist potency, except for 20a (R=CH3), which is the most potent antagonist of this series of compounds.
Tsotinis
Andrew
A
School of Pharmacy, University of Athens, Greece. tsotinis@pharm.uoa.gr
Vlachou
Margarita
M
Eleutheriades
Andreas
A
Prinea
Effie
E
Ebreo
Darren
D
The
Muy-Teck
MT
Sugden
David
D
D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008024:Ligands; D008547:Melanophores / Q000187:drug effects; D008550:Melatonin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000037:antagonists & inhibitors*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000037:antagonists & inhibitors*; D044094:Receptors, Melatonin; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D000081:Acetamides; D007211:Indoles; D008024:Ligands; C460544:N-(2-(1-(2-Phenethyl)-1H-indol-3-yl)ethyl)acetamide; C460559:N-(2-(5-Methoxy-1-(2-phenethyl)-1H-indol-3-yl)ethyl)acetamide; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D008550:Melatonin