Synthesis and anticonvulsant evaluation of some new 2-substituted-3-arylpyrido[2,3-d]pyrimidinones.
A series of 2-substituted-3-arylpyrido[2,3-d]pyrimidinones was prepared for evaluation as potential anticonvulsants. In murine screening, compounds 4a-c having a 2-oxo-2-(4-pyridyl)ethyl group in the 2-position and a 2-substituted phenyl moiety at the 3-position of the pyridopyrimidinone system displayed the most potent anti-seizure activity in both the maximal electroshock (MES) and pentylenetetrazol (scPTZ) tests at doses in the 3-10mg/kg range. Compound 4c showed no agonist activity at the GABA(A) receptor and was unable to block presynaptic sodium and calcium channels in vitro.
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0212, USA.
David C
DC
White
Thomas D
TD
Greenwood
Aaron L
AL
Downey
Jeffrey R
JR
Bloomquist
James F
JF
Wolfe
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000627:therapeutic use*; D051381:Rats; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; D011744:Pyrimidinones