Influence of amine substituents on 5-HT2A versus 5-HT2C binding of phenylalkyl- and indolylalkylamines.
The effect of 15 different amine substituents on 5-HT2A and 5-HT2C serotonin receptor binding was investigated for two series of compounds (i.e., phenylalkylamine and indolylalkylamine derivatives). In general, amine substitution decreases receptor affinity; however, N-(4-bromobenzyl) substitution results in compounds that bind at 5-HT2A receptors with high affinity (Ki < 1 nM) and with > 100-fold selectivity. Although parallel structural modification in the two series result in parallel shifts in 5-HT2C binding, these same modifications alter 5-HT2A binding in a less consistent manner.
Glennon
R A
RA
Department of Medicinal Chemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0540.
Dukat
M
M
el-Bermawy
M
M
Law
H
H
De los Angeles
J
J
Teitler
M
M
King
A
A
Herrick-Davis
K
K
D001665:Binding Sites; D002460:Cell Line; D005021:Ethylamines / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D007650:Ketanserin / Q000378:metabolism; D010627:Phenethylamines / Q000737:chemistry / Q000378:metabolism*; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
D005021:Ethylamines; D007211:Indoles; D010627:Phenethylamines; D011985:Receptors, Serotonin; D007650:Ketanserin