Solution phase parallel synthesis of substituted 3-phenylsulfonyl-[1,2,3]triazolo[1,5-a]quinazolines: selective serotonin 5-HT(6) receptor antagonists.
Here we present the solution phase parallel synthesis of a combinatorial library consisting of 776 new substituted 3-phenylsulfonyl-[1,2,3]triazolo[1,5-a]quinazolines and a study of the relation of their structure with a 5-HT(6) receptor antagonistic activity in a functional cell (HEK 293) analysis and radioligand competitive binding. We have found highly active and selective 5-HT(6)R antagonists. The most active 5-HT(6)R antagonists have IC(50) <100 nM in a functional assay, and K(i) <10 nM in a binding assay, which is 100 times higher than the activity with respect to other serotonin receptors.
Ivachtchenko
Alexandre V
AV
Chemical Diversity Research Institute, Russia.
Golovina
Elena S
ES
Kadieva
Madina G
MG
Koryakova
Angela G
AG
Kovalenko
Sergiy M
SM
Mitkin
Oleg D
OD
Okun
Ilya M
IM
Ravnyeyko
Irina M
IM
Tkachenko
Sergey E
SE
Zaremba
Oleg V
OV
D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000737:chemistry*; D054852:Small Molecule Libraries; D012996:Solutions; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011799:Quinazolines; D011985:Receptors, Serotonin; D054852:Small Molecule Libraries; D012996:Solutions; C097216:serotonin 6 receptor