title: 3,5-disubstituted 1,2,3,4-triazoles, 1 new  class of xanthine oxidase inhibitor.
abstract: 3,5-Bis(4-pyridyl)-1,2,4-triazole (PPT), 3-(4-pyrimidinyl)-5-(4-pyridyl)-1,2,4-triazole (PMPT), and 3-(4-pyridazinyl)-5-(4-pyridyl)-1,2,4-triazole (PZPT) are among the most active competitive inhibitors of xanthine oxidase among a series of 3,5-disubstituted triazoles synthesized for this purpose, inhibition constants being less than 1 times 10(-7) M for each. ED50 values in squirrel monkeys derived from first-order rate constants for the first and rate-limiting step of the sequence, xanthine leads to uric acid leads to allantoin plus CO2, range from 0.04 to 0.08 mg kg-1 orally, with unusually long durations of action attributable to asymmetric distribution of inhibitor within liver and gut as a consequence of enterohepatic recirculation. Sensitivity of rats, dogs, and anthropoid species to these, as to other xanthine oxidase inhibitors, is markedly less than that of the squirrel monkey, but the triazoles are at least an order of magnitude more active than the representative purine analogs tested.
mesh_terms: D000332:Aerobiosis; D000481:Allantoin / Q000096:biosynthesis; D000693:Anaerobiosis; D000818:Animals; D004285:Dogs; D004764:Enterohepatic Circulation; D005293:Ferritins / Q000378:metabolism; D000882:Haplorhini; D006922:Hylobates; D007042:Hypoxanthines / Q000378:metabolism; D007700:Kinetics; D010084:Oxidation-Reduction; D011119:Polynucleotides / Q000096:biosynthesis; D051381:Rats; D012453:Saimiri; D013045:Species Specificity; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014527:Uric Acid / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D007042:Hypoxanthines; D011119:Polynucleotides; D014230:Triazoles; D014527:Uric Acid; D000481:Allantoin; D005293:Ferritins; D014969:Xanthine Oxidase