1,2,3,4-tetrahydroisoquinoline derivatives: a new class of 5-HT1A receptor ligands.
Three series of new N-substituted 1,2,3,4-tetrahydroisoquinolines with 2-, 3-, and 4-membered alkyl chains (a, b, and c, respectively) were synthesized, and the effect of some structural modifications on their 5-HT1A receptor affinities and functional properties was discussed. It was found that the volume of the terminal amide substituent was a crucial parameter which determined 5-HT1A receptor affinities of the tested compounds, while the in vivo activity seemed to depend on both the R-volume and the length of a hydrocarbon chain. It was demonstrated that the most active ligands behaved like agonists or partial agonists at postsynaptic 5-HT1A receptors.
Mokrosz
M J
MJ
Department of Medicinal Chemistry, Polish Academy of Sciences, Kraków. mokroszm@rabbit.if-pan.krakow.pl
Bojarski
A J
AJ
Duszyńska
B
B
Tatarczyńska
E
E
Kłodzińska
A
A
Dereń-Wesołek
A
A
Charakchieva-Minol
S
S
Chojnacka-Wójcik
E
E
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000008:administration & dosage / Q000138:chemical synthesis*; D007700:Kinetics; D008046:Lip / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008956:Models, Chemical; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000145:classification; D012110:Reserpine / Q000494:pharmacology; D044005:Tetrahydroisoquinolines
D018759:Adrenergic Uptake Inhibitors; D007546:Isoquinolines; D011985:Receptors, Serotonin; D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D012110:Reserpine