title: Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam.
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.
authors.affiliation: Facultad 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
authors.forename: Adelfo
authors.initials: A
authors.lastname: Reyes
authors.forename: Leticia
authors.initials: L
authors.lastname: Huerta
authors.forename: Marisol
authors.initials: M
authors.lastname: Alfaro
authors.forename: Andrés
authors.initials: A
authors.lastname: Navarrete
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D054833:Isoindoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D010889:Piracetam / Q000737:chemistry* / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: C110621:Isoindol-1-one; D054833:Isoindoles; D018697:Nootropic Agents; D012601:Scopolamine; D010889:Piracetam