Synthesis and research of benzylamides of some isocyclic and heterocyclic acids as potential anticonvulsants.
A series of benzylamides of isocyclic and heterocyclic acids was synthesized and tested in Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Near all synthesized derivatives of heterocyclic acids showed activity. All obtained derivatives of mono- and bicyclic isocyclic acids were inactive. The power of action of heterocyclic acids derivatives seems does not depend upon kind of heteroatom (N, O or S). One of the compounds (2-furoic acid benzylamide (4)) appeared most promising. It showed in minimal clonic seizure (6Hz) test (ASP) in rats after i. p. administration: MES ED50 = 36.5 mg/kg, TOX TD50 = 269.75 mg/kg, and PI = 7.39.
Department of Drug Chemistry, Warsaw Medical University, 02-097 Warszawa, Poland.
Marzanna
M
Strupińska
Grazyna
G
Rostafińska-Suchar
Elzbieta
E
Pirianowicz-Chaber
James P
JP
Stables
Jeff
J
Jiang
Ryszard
R
Paruszewski
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D015394:Molecular Structure; D010862:Pilocarpine; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013329:Structure-Activity Relationship
D000577:Amides; D000927:Anticonvulsants; D001593:Benzyl Compounds; D010862:Pilocarpine