Synthesis and cognition-activating properties of some mono- and bicyclic lactam derivatives

Abstract

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.

Dearomatization of 3,5-dinitropyridines – an atom-efficient approach to fused 3-nitropyrrolidines

“…It should be noted that hydrogenated pyrrolo [3,4-c]pyridine core is an important scaffold since compounds of this class possess antibacterial 32 , and anticancer activity 33,34 as well as cognition activating properties. 35 The structures of compounds 7a-e were confirmed by NMR-spectroscopy and HRMS data, as well as X-ray diffraction study (for compounds 7a,b,e). It was found that addition of two molecules of the dipole occurs from the opposite sides of the pyridine ring.…”

Synthesis of cis-perhydropyrrolo[3,4-c]pyridine-3,4-dione and Its X-ray Structure

“…In [2], the reductive cyclization reaction was conducted under hydrogen at 100 °C and 100 atm pressure for 48h by one-pot method. We have the work coming from two steps: the reductive experiment should be made under hydrogen at 60°C and 45 atm pressure for 12 h and after filtration and stripping of the solvent, the final cyclization step was conducted in toluene at 120°C in the same autoclave to avoid high pressure.…”

“…The cognition activating properties of cis-perhydropyrrolo [3,4-c]pyridine-3,4-dione was evaluated in enhancing retention for passive avoidance learning in rats. It was also found to be more potent than piracetam in the amnesiareversal testing [2].…”

“…The incidence of cognitive disorders in the population is likely to grow [1], therefore, it is significant to research and develop an effective nootropic drug for the people who need necessary medical care. Cosimo Altomare et al [2] synthesized some mono-and bi-cyclic lactam derivatives by reductive cyclization reactions under the condition of high pressure. The cognition activating properties of cis-perhydropyrrolo [3,4-c]pyridine-3,4-dione was evaluated in enhancing retention for passive avoidance learning in rats.…”

Towards Better Brain Management: Nootropics

“…However, the vast majority of the active compounds conserve the 2-oxopyrrolidine ring. This ring has been successfully substituted in almost every position, but compounds where the pyrrolidine ring has been condensed with other rings are rare [110,111].…”