Synthesis of 2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole derivatives and their central nervous system activities

Abstract

The synthesis and some pharmacological effects of cis- and trans-2-substituted 2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole derivatives are described. In these derivatives, the substituents of the 2, 5 and 8 position, together with the relative configuration of the 4a and 9b position, influenced the potency of the central nervous system activities. A cis-2-[3-(p-fluorobenzoyl)propyl] analogue (5k) of carbidine (1) possessed not only thymoleptic-like biological activity but had more potent neuroleptic activity than the parent drug.

γ-Carbolines and their hydrogenated derivatives 3.* Hydrogenated derivatives of γ-carbolines: chemical and biological poperties (Review)

“…For example, cis-2,8-dimethyl-1,2,3,4,4a,9b-hexahydro-γ-carboline (Carbidine) is effective in the treatment of schizophrenia, alcohol psychoses, and withdrawal syndromes [186]. cis-2-[3-(p-Fluorobenzoyl)propyl]-8-methyl-1,2,3,4,4a,9b-hexahydro-γ-carboline has similar activity [187].…”

γ-Carbolines and their hydrogenated derivatives. 2.* Hydrogenated derivatives of γ-carbolines: methods of synthesis (review)

“…This is evidently due to the fact that the formed complex of borane with the secondary amine is hydrolyzed significantly more quickly than with the tertiary amine; in this case the hydrolysis can take place earlier than protonation of the indole ring and subsequent hydride transfer [137]. This is why reduction of the N-benzyl-substituted derivatives followed by catalytic debenzylation was used for the production of secondary trans isomers of hexahydro-γ-carbolines [122]. However, the use of CF 3 COOH (strong enough for the formation of the 3H-indolinium ion and the non-nucleophilic acid) makes it possible to obtain trans-hexahydro-γ-carbolines containing a secondary amino group at position 2 with yields greater than 80% by direct reduction [138].…”

“…cis-1,2,3,4,4a,9b-Hexahydro-γ-carbolines can be obtained by catalytic hydrogenation of the corresponding tetrahydro-γ-carbolines over PtO 2 in dilute hydrochloric acid [122]. The method is not used often on account of the need for special equipment; moreover, the complexity of catalytic hydrogenation again involves the possibility of more extensive reduction, and it is not always possible to stop at the formation of the hexahydro-γ-carboline.…”

Extraction and chromatographic separation methods in pharmacokinetic studies of Stobadine�?an indole-related antioxidant and free-radical scavenger

“…Their chemical structure indicated that in the Stobadine molecule the position of 2-N (cf. To prepare the anticipated Stobadine metabolites, knowledge derived from the synthesis of some other 2,3,4,4a.5.9b-hexahydro-1Hpyrido[4,3-b]indole derivatives was exploited (Nagai et al, 1979). 1) was enzymatically attacked.…”