title: Synthesis and anticonvulsant activity of novel 2,6-diketopiperazine derivatives. Part 1: perhydropyrrole[1,2-a]pyrazines.
abstract: A number of novel pyrrole[1,2-a]pyrazine derivatives were synthesized and evaluated in in vivo animal models of epilepsy. Among them, several compounds displayed promising seizure protection in the maximal electroshock seizure (MES), subcutaneous metrazol seizure (scMET), 6 Hz and pilocarpine-induced status prevention (PISP) tests, with ED(50) values comparable to the reference anticonvulsant drugs (AEDs). A critical influence of the stereochemistry and conformational preferences of the pyrrole[1,2-a]pyrazine core on in vivo pharmacological activity was observed. The mechanism of the anticonvulsant action of the agents synthesized is most probably not via inhibition of the voltage-dependent sodium (Na(+)) currents.
authors.affiliation: Department of Drug Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Str., 02-097 Warszawa, Poland. maciej.dawidowski@wum.edu.pl
authors.forename: Maciej
authors.initials: M
authors.lastname: Dawidowski
authors.forename: Franciszek
authors.initials: F
authors.lastname: Herold
authors.forename: Andrzej
authors.initials: A
authors.lastname: Chodkowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kleps
authors.forename: Paweł
authors.initials: P
authors.lastname: Szulczyk
authors.forename: Marcin
authors.initials: M
authors.lastname: Wilczek
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D054659:Diketopiperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D004597:Electroshock; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D026941:Sodium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D054659:Diketopiperazines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D010433:Pentylenetetrazole