Synthesis and structural studies of aza analogues of functionalized amino acids: new anticonvulsant agents.
We have reported that functionalized amino acids 1 display potent anticonvulsant activities in mice and rats, and that the activity resides primarily in the D-isomer. In this study we investigated whether selectively replacing the C(2) tetrahedral atom with a trivalent nitrogen provides compounds with comparable activity. Six functionalized N(2)-substituted semicarbazides (3) were prepared. X-ray crystallographic analysis of 1-acetyl-4-benzyl-2-(thiazol-2-yl)semicarbazide (13) showed that it lost asymmetry and adopted a configuration midway between the corresponding D- and L-amino acid derivatives. Evaluation of 3 in both mice (ip) and rats (po) showed that the compounds exhibited significant anticonvulsant activities but in most cases at levels lower than their amino acid counterparts. One of the semicarbazides, 13, displayed excellent activity in mice and rats that compared favorably to that of phenytoin.
Andurkar
S V
SV
Department of Chemistry, University of Houston, Houston, Texas 77204-5641, USA.
Béguin
C
C
Stables
J P
JP
Kohn
H
H
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004597:Electroshock; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D012640:Seizures / Q000188:drug therapy; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
C425788:1-acetyl-4-benzyl-2-(thiazol-2-yl)semicarbazide; D000927:Anticonvulsants; D001372:Aza Compounds; D012663:Semicarbazides