1,2,3,4-Tetrahydroisoquinoline Derivatives: A New Class of 5-HT 1A Receptor Ligands 1Part 34 of the series: structure–activity relationship studies of CNS agents. 1

New Imide 5-HT1A Receptor Ligands – Modification of Terminal Fragment Geometry

“…Although THIQ itself does not show any affinity for the 5-HT 1A receptors (K i > 50 000 nM) [12] its substitution with butylazaspiro [4.5]decane-7,9-dione (MM199, Figure 1) increased the affinity to nanomolar level [9]. The same was observed in the case of the 1-adamantoyloaminobutyl THIQ derivative, for which K i = 0.95 nM was determined [13]. It was then concluded that bulky alicyclic termini should be especially well accommodated by the 5-HT 1A binding site.…”

Silyl modification of biologically active compounds. 11. Synthesis, physico‐chemical and biological evaluation of N‐(trialkoxysilylalkyl)tetrahydro(iso,silaiso) quinoline derivatives

“…6,7 According to the literature data, some quinoline or tetrahydroquinoline ringcontaining compounds possess antiproliferative activity by inhibition of topoisomerase II 8,9 or topoisomerase I, 10 or have cytostatic effects. 11,12 It has been reported that tetrahydro(iso)quinoline based compounds display affinity to serotonin (5-HT 1A ), 13,14 dopamine 15 and NMDA receptors, 16 and possess sedative properties. 17 Neurotropic properties of tetrahydro(iso, silaiso)quinoline derivatives were confirmed by investigation.…”

Benzolactam Derivatives and Their Affinity for α1- and α2- Adrenoreceptors

“…Three elements of 4-substituted 1-arylpiperazines, namely the 1-aryl substituent [1] , the terminal fragment (frequently an amide or imide moiety [2] ), and the alkyl spacer linking the amide with the piperazine [3,4] influence the affinity and selectivity of this most thoroughly studied class of ligands. However, in recent years 1,2,3,4-tetrahydroisoquinoline (THIQ) arouses increasing interest as a basic element of serotonin 5-HT 1A receptor ligands [5] or, directly, as a ligand of α 2 -AR (adrenergic) receptors [6] . This molecule, which is inactive at 5-HT 1A receptor binding sites (K i >50 000 nM), when modified by 2-(ω-amide)alkyl substituents can form potent 5-HT 1A receptor ligands [5] .…”

“…However, in recent years 1,2,3,4-tetrahydroisoquinoline (THIQ) arouses increasing interest as a basic element of serotonin 5-HT 1A receptor ligands [5] or, directly, as a ligand of α 2 -AR (adrenergic) receptors [6] . This molecule, which is inactive at 5-HT 1A receptor binding sites (K i >50 000 nM), when modified by 2-(ω-amide)alkyl substituents can form potent 5-HT 1A receptor ligands [5] . On the other hand, its moderate α 1 and α 2 binding constants (14, K i = 1780 nM, and 350 nM [6] , respectively) suggest that, like arylpiperazines, THIQ can be a starting molecule for designing α 1 and/or α 2 ligands.…”