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.
White
David C
DC
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0212, USA.
Greenwood
Thomas D
TD
Downey
Aaron L
AL
Bloomquist
Jeffrey R
JR
Wolfe
James F
JF
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