Cyanopyrazoles as analogs of purine precursors--I. Inhibitory effect on purine biosynthesis de novo.
The in vitro inhibition of purine biosynthesis de novo by a series of cyanopyrazoles was studied. At concentration 1 mM trichloromethyl analogs (3(5)-amino-4-cyano-5(3)-trichloromethylpyrazole and N-hydroxyethyl-3(5)-amino-4-cyano-5(3)-trichloromethylpyrazole) were found to inhibit IMP synthesis 80 and 30% respectively. GAR synthesis was inhibited at a lower degree at the same range of concentrations. The compounds demonstrated a similar pattern of inhibition of the last steps, e.g. AICAR formylation and cyclization as found on the whole pathway.
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D010856:Columbidae; D066298:In Vitro Techniques; D007291:Inosine Monophosphate / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D011687:Purines / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology*; D012265:Ribonucleotides / Q000096:biosynthesis / Q000378:metabolism
D009570:Nitriles; D011687:Purines; D011720:Pyrazoles; D012265:Ribonucleotides; C014978:glycineamide ribonucleotide; D007291:Inosine Monophosphate; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide