Synthesis and cognition activating properties of some mono- and bicyclic lactam derivatives.
Upon reductive cyclization cyano esters 2, 3, and 9 yielded piperidones and perhydropyrrolo[3,4-c]pyridine lactams, generally as a mixture of diasteromeric cis-trans forms. X-ray crystallographic analyses were carried out on bicyclic dilactam derivatives 6 and 10, and a cis configuration at the ring junction was determined in both cases. A series of neuropsychopharmacological tests performed on the title compounds indicated that they are generally nontoxic even at high doses (up to 1000 mg/kg ip). The cognition activating properties of lactams 4, 5, 6, and 10 were evaluated in enhancing retention for passive avoidance learning in rats without and after electroconvulsive shock (ECS); compounds 5 and 10 were found to be more potent than piracetam in the amnesia-reversal testing.
Altomare
C
C
Dipartimento Farmaco-Chimico, University of Bari, Italy.
Carotti
A
A
Casini
G
G
Cellamare
S
S
Ferappi
M
M
Gavuzzo
E
E
Mazza
F
F
Pantaleoni
G
G
Giorgi
R
R
D000647:Amnesia / Q000517:prevention & control; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D003071:Cognition / Q000187:drug effects*; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D014961:X-Ray Diffraction
D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D007769:Lactams