Synthesis and anticonvulsant activity of some amino acid derivatives. Part 1: alanine derivatives.
Fifteen amides of N-substituted D-Ala, DL-Ala and beta Ala have been designed and synthesized as potential anticonvulsants. All obtained amides as well as one intermediate (8) were evaluated in the maximal electroshock seizure (MES) test, the subcutaneous Metrazol seizure threshold (sc Met) test and the rotorod neurotoxicity (Tox) test in mice. According to the classification of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) eight compounds received class I, three class II and five class III designations. Two of the most active compounds (20, 24) were tested quantitatively. They exhibited, after i.p. administration in mice, a large protective index (PI) 3.2 for 20 and 4.3 for 24 and after oral administration in rat PI > 18 for 20 and > 14 for 24.
Department of Pharmaceutical Chemistry, Medical University, Warszawa, Poland.
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R
Paruszewski
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Rostafinska-Suchar
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Strupinska
P
P
Jaworski
J P
JP
Stables
D000107:Acetylation; D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003292:Convulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004597:Electroshock; D005684:Gait / Q000187:drug effects; D007274:Injections, Intraperitoneal; D051379:Mice; D009949:Orientation / Q000187:drug effects; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D012640:Seizures / Q000517:prevention & control
D000927:Anticonvulsants; D003292:Convulsants; D000409:Alanine; D010433:Pentylenetetrazole