Discovery of 5-arylsulfonamido-3-(pyrrolidin-2-ylmethyl)-1H-indole derivatives as potent, selective 5-HT6 receptor agonists and antagonists.
5-Arylsulfonylamido-3-(pyrrolidin-2-ylmethyl)-1H-indoles have been identified as high-affinity 5-HT(6) receptor ligands. Within this class, several of the (R)-enantiomers were potent agonists having EC(50) values of 1 nM or less and functioning as full agonists while the (S)-enantiomers displayed moderate antagonist activity.
Cole
Derek C
DC
Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA. coledc@wyeth.com
Lennox
William J
WJ
Lombardi
Sabrina
S
Ellingboe
John W
JW
Bernotas
Ronald C
RC
Tawa
Gregory J
GJ
Mazandarani
Hossein
H
Smith
Deborah L
DL
Zhang
Guoming
G
Coupet
Joseph
J
Schechter
Lee E
LE
D000242:Cyclic AMP / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D007211:Indoles; D011759:Pyrrolidines; D011985:Receptors, Serotonin; D013449:Sulfonamides; C097216:serotonin 6 receptor; D000242:Cyclic AMP