Synthesis of novel isoquinoline derivatives as potential CNS‐agents

Abstract

A series of 4‐aminomethyl‐1,2,3,4‐tetrahydroisoquinoline derivatives were prepared as potential CNS‐agents acting via amino‐acid neurotransmitter systems. The compounds were synthesized from 1,2,3,4‐tetra‐hydro‐1‐oxoisoquinoline‐4‐carboxylic acids obtained by dipolar cycloaddition reactions of imines with homo‐phthalic anhydride. Among the compounds tested 5c and 5m showed sub‐micromolar affinity for the NMDA receptor and represent a structurally novel class of ligand for this site.

Synthesis and anticonvulsant properties of 1,2,3,4-tetrahydroisoquinolin-1-ones

“…On the contrary, in some cases using more drastic conditions (i.e boiling toluene), the reaction mixture afforded trans-diasteroisomer. As previously reported 30 this latter can be recovered by isomerization of cis-isomer on heating in acetic acid (e.g. 9e).…”

“…[28][29][30][31] The products 9 possess two asymmetric centres (C-3 and C-4) and therefore could exist as cis-or trans-diastereoisomers. When we treated the suitable imine 7a-k with homophthalic anhydride 8a-k in chloroform at room temperature, only the cis diastereoisomer was generally recovered.…”

Synthesis and a Configurational Correlation within cis- and trans- Oxazolotetrahydroisoquinolinones with an Angular Substituent

“…When acid cis-8 was treated with potassium carbonate in dry DMF, complete epimerization was established yielding acid trans-8, which was further converted to ester trans-9 by reaction with methyl iodide (Scheme 3A) [14,15]. Treatment of a mixture of acids trans-8 and cis-8 with potassium carbonate and methyl iodide in dry DMF afforded only ester trans-9 (Scheme 3B).…”

Synthesis of New trans-2-Benzyl-3-(furan-2-yl)-4-substituted-1,2,3,4-tetrahydroisoquinolinones

“…Substituted 1,2,3,4-tetrahydroisoquinolines are important because of their occurrence in nature [1,2] and their pharmacological properties [3][4][5][6]. Several methods have been described for preparation of tetrahydroisoquinolines [7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

“…Moreover, attention was paid to the transformation of the products of type 1 into various compounds of type 2 having a cyclic aminomethyl group in position 4 of the tetrahydroisoquinolinone ring. The presence of the fragment given in bold in 2 is the source of their potential biological activity [5] that can be modified by the presence of other pharmacophoric groups.…”