N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists.
A series of N(1)-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)indole derivatives was designed and synthesized. These compounds were shown to have high affinity for the 5-HT(6) receptor. Two analogs, 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-1-sulfonyl]-phenylamine 15g and 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-5-methoxy-1H-indole-1-sulfonyl]-phenylamine 15y, had 0.4 and 3.0 nM affinity, respectively, and antagonized the production of adenylate cyclase at sub-nanomolar concentrations.
Cole
Derek C
DC
Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. coledc@wyeth.com
Ellingboe
John W
JW
Lennox
William J
WJ
Mazandarani
Hossein
H
Smith
Deborah L
DL
Stock
Joseph R
JR
Zhang
Guoming
G
Zhou
Ping
P
Schechter
Lee E
LE
D000262:Adenylyl Cyclases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor; D000262:Adenylyl Cyclases