The binding of arylguanidines at 5-HT(3) serotonin receptors: a structure-affinity investigation.
The 5-HT(3) receptor binding affinities of nine pairs of aryl-substituted arylguanidines and arylbiguanides were examined and the results suggest the likelihood that both classes of agents utilize common receptor binding features. The effects of structural modification were also examined using CoMFA. 1-(3,4,5-Trichlorophenyl)guanidine (5-HT(3) K(i)=0.7 nM) was identified as a very high-affinity arylguanidine. The structures of the high-affinity arylguanidines are inconsistent with current 5-HT(3) pharmacophore models.
Dukat
M
M
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
Choi
Y N
YN
Teitler
M
M
Du Pre
A
A
Herrick-Davis
K
K
Smith
C
C
Glennon
R A
RA
D000818:Animals; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism*; D006822:Hybrid Cells; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000737:chemistry / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D006146:Guanidines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists