Synthesis and 5-HT3 affinity of new 3-substituted indoles at central nervous system.
A series of 3-imino and 3-aminomethyl-N-methylindoles, in which the amine substituents were 3-quinuclidyl and 1-adamantyl groups, were synthesized and their in vitro affinity towards 5-HT3 central receptors evaluated. Of the nine compounds tested, three caused displacement of 3H-BRL 43694 binding to 5-HT3. 2-Chloro-3-(3-quinuclidylimino)-1-methylindole, 4, was the most potent compound with an IC50 = 5.15 10(-8) M. Moreover, the monoamine oxidase inhibition activity was tested and three compounds were shown to be MAO inhibitors, their IC50 was in the range of that of (-)-Deprenyl. Again, 4 was the most potent compound. Structure-activity relationships within the series are briefly discussed.
Monge
A
A
CIFA, Department of Medicinal Chemistry, Universidad de Navarra, Pamplona, Spain.
Palop
J A
JA
Orts
L
L
Oset
C
C
Lasheras
B
B
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3
C105745:2-chloro-3-(3-quinuclidylimino)-1-methylindole; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D011812:Quinuclidines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3