N1-(Benzenesulfonyl)tryptamines as novel 5-HT6 antagonists.
N-Benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine (BS/5-OMe DMT; 5) was shown to bind at human 5-HT6 serotonin receptors with high affinity (Ki = 2.3 nM) relative to serotonin (Ki = 78 nM). Structural variation failed to result in significantly enhanced affinity. BS/5-OMe DMT acts as an antagonist of 5-HT-stimulated adenylate cyclase (pA2 = 8.88 nM) and may represent the first member of a novel class of 5-HT6 antagonists.
Tsai
Y
Y
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0540, USA.
Dukat
M
M
Slassi
A
A
MacLean
N
N
Demchyshyn
L
L
Savage
J E
JE
Roth
B L
BL
Hufesein
S
S
Lee
M
M
Glennon
R A
RA
D000262:Adenylyl Cyclases / Q000378:metabolism; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection; D014363:Tryptamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C419803:N1-benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D014363:Tryptamines; C097216:serotonin 6 receptor; D000262:Adenylyl Cyclases