Conformational theoretical study of substituted and non-substituted N-aralkyl-2-aminoindans and its relation with dopaminergic activity
Ab initio molecular orbital calculations are presented for two isomers of nine derivatives from 2-aminoindan. The study is centered in the geometrical analysis of the structures with adequate conformation to interact with the dopaminergic receptor. Pharmacological test performed on four out on the nine racemic and diastereoisomeric mixture studied in the present paper, indicated that the presence of the hydroxyl groups in the aminoindan ring is necessary for the agonist effect, whereas the compounds with hydroxyl groups in the aralkyl ring cause an antagonist effect. The theoretical calculations show that only the isomers RR have the suitable geometry to allow such interactions in the receptor cavity. This is a consequence of the fact that the RR isomers show greater planarity than the RS ones, so the former fill up the dopaminergic receptor. Small differences in some inter-atomic distances and diverse values of dipolar moment were responsible for the activity in this coupled compound-receptor model. On the other hand, the total energy values were very similar, but the RR isomers energy was always slightly lower than that of the RS isomers. The gap values (HOMO-LUMO) did not show significant differences among the compounds; however, for the RS isomers they were slightly higher than those of the RR isomers. Thus, the RS isomers were slightly more reactive than the RR ones. © 2003 Published by Elsevier B.V.
Rodríguez, LJ; Medina, Y; Suárez-Roca, H; De Angel, BM; Israel, A; Charris, JE; López, SE; Caldera, JA; Angel-Guio, JE
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