Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with
Adelfo Reyes1, Leticia Huerta, Marisol Alfaro
1Facultad de Estudios Superiores Zaragoza, Unidad Multidisciplinaria de Investigación Experimental, Universidad Nacional Autónoma de México, Batalla 5 de Mayo esquina Fuerte de Loreto, Ejército de Oriente, Iztapalapa, México D. F., México. adelfo@puma2.zaragoza.unam.mx
Abstract:
Three 2,3-dihydro-1H-isoindol-1-ones structurally related with piracetam (=2-oxopyrrolidine-1-acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)-2, (R,R)-3, and (R,S)-3 were obtained in good yields in only two steps starting from methyl DL-phthaloylalanine. Compound (RS)-2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)-3 and (R,S)-3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)-3 showed lower efficacy than (R,R)-3. Only (R,R)-3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor-coordination effect in mice. These synthesized 2,3-dihydro-1H-isoindol-1-one derivatives constitute a new kind of nootropic compounds.
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