Synthesis and anticonvulsant activity of some amino acid derivatives. Part 2: Derivatives of Gly, Ala, Leu, Pro, Trp, Phe(4 Cl), Ala(alpha-Me).
Fourteen amides of N-substituted natural and anatural amino acids have been designed and synthesized as potential anticonvulsants. They were evaluated in the maximal electroshock seizure (MES) test, the subcutaneous Metrazol seizure threshold (sc Met) test and the rotorod neurotoxicity (Tox) test. According to the classification of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) eight of synthesized compounds received class I, two class II and four class III. One of the compounds classified in class I (18) was tested quantitatively after i.p. administration in mice. It showed MES ED50 = 67.41 mg/kg and protective index (PI) = 4.5. Conformational models of the synthesized compounds were compared to one another, as well as to models of some standard compounds.
Paruszewski
R
R
Department of Pharmaceutical Chemistry, Medical University, Warszawa, Poland.
Rostafinska-Suchar
G
G
Strupinska
M
M
Jaworski
P
P
Winiecka
I
I
Stables
J P
JP
D000596:Amino Acids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004597:Electroshock; D007274:Injections, Intraperitoneal; D051379:Mice; D008968:Molecular Conformation; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D004856:Postural Balance / Q000187:drug effects; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000927:Anticonvulsants; D010433:Pentylenetetrazole