N1-benzenesulfonylgramine and N1-benzenesulfonylskatole: novel 5-HT6 receptor ligand templates.
1-Benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine (3; K(i)=2.3 nM) is a 5-HT(6) receptor antagonist; removal of the 5-methoxy group (i.e., 6; K(i)=4.1 nM) has little impact on receptor affinity. In the present study, it is shown that the aminomethyl portion of 6 can be shortened to gramine analogue 10a (K(i)=3.1 nM); a related skatole derivative 11b (K(i)=12 nM) also binds with high affinity indicating that the aminoethyl portion of the tryptamines is not required for binding. Compounds 10a and 11b represent members of novel classes of 5-HT(6) antagonists.
Pullagurla
Manik R
MR
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
Dukat
Małgorzata
M
Setola
Vincent
V
Roth
Bryan
B
Glennon
Richard A
RA
D001555:Benzene Derivatives / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D011985:Receptors, Serotonin / Q000378:metabolism*; D014363:Tryptamines / Q000737:chemistry* / Q000378:metabolism*
D001555:Benzene Derivatives; D008024:Ligands; D011985:Receptors, Serotonin; D014363:Tryptamines; C097216:serotonin 6 receptor