Specificity in enzyme inhibition. 3. Synthesis of 5-substituted 2,2-dimethyl-4-imidazolidinones as inhibitors of tyrosine decarboxylase and histidine decarboxylase.
2,2-Dimethyl-4-imidazolidinone derivatives of the alpha-amino acids DL-phenylglycine (1), DL-phenylalanine (2), L-tyrosine (3), L-histidine (4), and L-tryptophan (5) were prepared in order to assess their specificity in inhibiting amino acid decarboxylases. Treatment of th alpha-aminonitriles with acetone in the presence of base and heat or treatment of the alpha-amino amides with acetone gave the title compounds in 48-85% yield. The compounds afforded moderate ability to inhibit the decarboxylation of L-phenylalanine, L-tyrosine, or L-histidine in vitro, using crude enzymes. 3 was a better inhibitor of tyrosine decarboxylase (S. faecalis) than 2. 4 and 5 were comparable to 3 in inhibiting tyrosine decarboxylase. 4 was more selective in inhibiting purified histidine decarboxylase (Cl. welchii) than 5, which was inactive. 4 was inactive against fetal rat histidine decarboxylase in vitro.
D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D003016:Clostridium perfringens / Q000201:enzymology; D013293:Enterococcus faecalis / Q000201:enzymology; D005333:Fetus / Q000201:enzymology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D010649:Phenylalanine; D051381:Rats; D014445:Tyrosine Decarboxylase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D010649:Phenylalanine; D002262:Carboxy-Lyases; D006640:Histidine Decarboxylase; D014445:Tyrosine Decarboxylase