A. Bojarski, S. Misztal, J. Boksa
2001
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Journal
Medicinal Chemistry Research
Abstract
Two series of 2-butyl-8-azaspiro[5,4]decane-7,9-dione (a) and N-phthalimidobutyl (b) derivatives of 1,2,3,4-tetrahydroisoquinoline (THIQ) were synthesized. The impact of substituent variations in the aromatic part of the THIQ moiety on 5-HT 1 A and 5-HT 2 A receptor affinities, as well as in vivo functional properties of the investigated compounds are discussed. It was found that those modifications improved 5-HT 2 A receptor affinity, but also slightly reduced the binding affinity for 5-HT 1 A receptors (in comparison with the unsubstituted THIQ derivatives 3a and 3b). The most active compound (8-Br,5-OCH 3 -THIQ - 8a) showed features of a 5-HT 1 A (postsynaptic)/5-HT 2 A receptor antagonist. Additionally, all chloro derivatives with high and equal affinity for 5-HT 1 A receptors revealed different functional properties, i.e. an agonistic activity of presynaptic 5-HT 1 A receptors (4a) and a partial agonistic activity of postsynaptic 5-HT 1 A receptors (4a, 6a) or an antagonistic activity of postsynaptic ones (5a).