Identification of novel indanylsulfonamide guanylhydrazones as potent 5-HT6 serotonin receptor antagonists.
Changing the N,N-(dimethylamino)ethyl side chain in the N-[3-(aminoethyl)inden-5-yl]sulfonamide 5-HT(6) serotonin receptor agonists 1 by a conformationally rigid guanylhydrazone moiety at the indene 3-position led to the identification of the title indanylguanylhydrazones 6, which exhibited excellent binding affinities and an antagonistic response at the 5-HT(6) receptor, with K(i) and IC(50) values in the nanomolar range (K(i) >or= 1.2 nM, IC(50) >or= 47 nM, and I(max) <or= 173%).
Mesquida
Neus
N
Departament de Farmacologia i Química Terapeutica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain. neusmesquida@ub.edu
López-Pérez
Sara
S
Dinarès
Immaculada
I
Frigola
Jordi
J
Mercè
Ramon
R
Holenz
Jörg
J
Pérez
Raquel
R
Burgueño
Javier
J
Alcalde
Ermitas
E
D006157:Guanosine Monophosphate / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D007192:Indenes; D020128:Inhibitory Concentration 50; D011485:Protein Binding; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
D006835:Hydrazones; D007192:Indenes; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; C097216:serotonin 6 receptor; D006157:Guanosine Monophosphate