5-Cyclic amine-3-arylsulfonylindazoles as novel 5-HT6 receptor antagonists.
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.
Haydar
Simon N
SN
Wyeth Research, CN 8000, Princeton, New Jersey 08543, USA. Haydars@wyeth.com
Yun
Heedong
H
Andrae
Patrick M
PM
Mattes
James
J
Zhang
Jean
J
Kramer
Angela
A
Smith
Deborah L
DL
Huselton
Christine
C
Graf
Radka
R
Aschmies
Suzan
S
Schechter
Lee E
LE
Comery
Thomas A
TA
Robichaud
Albert J
AJ
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006801:Humans; D007191:Indazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008956:Models, Chemical; D015394:Molecular Structure; D051381:Rats; D044403:Receptor, Serotonin, 5-HT2B / Q000737:chemistry / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D007191:Indazoles; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D013450:Sulfones; C097216:serotonin 6 receptor