Abstract
Novel 5-cyclic amine-3-arylsulfonylindazoles were prepared, and several analogues within this class have been identified as high-affinity 5-HT(6) receptor ligands with improved pharmacokinetic and pharmacological properties. One selected example, 18b, showed good brain penetrability and a generally favorable pharmacokinetic profile with procognitive efficacy in the rat novel object recognition assay. The synthesis and structure-activity relationship of this potent class are discussed.
MeSH terms
-
Animals
-
Binding, Competitive
-
Brain / metabolism
-
Exploratory Behavior / drug effects
-
Habituation, Psychophysiologic / drug effects
-
Humans
-
Indazoles / chemistry
-
Indazoles / metabolism*
-
Indazoles / pharmacology
-
Models, Chemical
-
Molecular Structure
-
Rats
-
Receptor, Serotonin, 5-HT2B / chemistry
-
Receptor, Serotonin, 5-HT2B / metabolism
-
Receptors, Serotonin / chemistry
-
Receptors, Serotonin / metabolism*
-
Recognition, Psychology / drug effects
-
Serotonin 5-HT2 Receptor Antagonists
-
Serotonin Antagonists / chemistry
-
Serotonin Antagonists / metabolism*
-
Serotonin Antagonists / pharmacokinetics
-
Structure-Activity Relationship
-
Sulfones / chemistry
-
Sulfones / metabolism*
-
Sulfones / pharmacology
Substances
-
Indazoles
-
Receptor, Serotonin, 5-HT2B
-
Receptors, Serotonin
-
Serotonin 5-HT2 Receptor Antagonists
-
Serotonin Antagonists
-
Sulfones
-
serotonin 6 receptor