Synthesis and 5-hydroxytryptamine antagonist activity of 2-[[2-(dimethylamino)ethyl]thio]-3-phenylquinoline and its analogues.
A series of 2-[(2-aminoethyl)thio]quinolines substituted at the 3-position with alkyl, aryl, or heteroaryl groups has been prepared in the search for novel and selective 5-HT2 antagonists. The affinity of the compounds for 5-HT1 receptor sites was measured by their ability to displace [3H]-5-HT from rat brain synaptosomes whereas the affinity for 5-HT2 receptor sites was measured by their ability to displace [3H]spiperone from synaptosomes prepared from rat brain cortex. The 5-HT2 antagonist properties of the compounds were measured in vivo by their antagonism of 5-hydroxytryptophan-induced head twitches in the mouse and by their antagonism of hyperthermia induced by fenfluramine (N-ethyl-alpha-methyl-m-(trifluoromethyl)phenethylamine hydrochloride) in the rat. The structure-activity relationships in this series are discussed and the properties of 2-[[2-(dimethylamino)ethyl]thio]-3-phenylquinoline hydrochloride (70) are highlighted.
Blackburn
T P
TP
ICI Pharmaceuticals Division, Research Department 2, Macclesfield, Cheshire, U.K.
Cox
B
B
Guildford
A J
AJ
Le Count
D J
DJ
Middlemiss
D N
DN
Pearce
R J
RJ
Thornber
C W
CW
D000818:Animals; D005260:Female; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D051379:Mice; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D011804:Quinolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline; D008729:Methoxamine