CNS depressant activity of pyrimidylthiazolidones and their selective inhibition of NAD-dependent pyruvate oxidation.

Several 1-aryl-3-(2-pyrimidyl)thiocarbamides and their corresponding cyclized 2-arylimino-3-(2-pyrimidyl)thiazolid-4-ones were synthesized and characterized by their sharp melting points and elemental analyses. These thiocarbamides and thiazolidones possessed anticonvulsant activity against pentylenetetrazol-induced convulsions and potentiated pentobarbital-induced hypnosis in mice. Most of these thiocarbamides and thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, where the use of added NAD dether hand, remained unaltered. The anticonvulsant activity of thiocarbamides and thiazolidones was unrelated to their ability to inhibit the respiratory activity of rat brain homogenates during oxidation of sodium pyruvate. Cyclization of thiocarbamides to the corresponding thiazolidones in general enhanced their CNS depressant and enzyme inhibitory effectiveness.