Novel xanthine oxidase inhibitor studies. Part 3. Convenient and general syntheses of 3-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidin-5(6H)-ones as a new class of potential xanthine oxidase inhibitors

Abstract

Convenient and general syntheses of 3-substituted 7H-pyrazolo[4,3-e]-1,2,4-triazolo[4,3-c]pyrimidin-5(6H)-ones (12), a new class of potent xanthine oxidase inhibitors, involving the oxidative cyclisation of 6-substituted 4-alkylidenehydrazino- or 4-arylmethylidenehydrazino-1H-pyrazolo[3,4-d]pyrimidines (3 and 11) with 70% nitric acid as the key step, are reported. The hydrazones 3 and 11 were obtained by a versatile synthetic route via the key intermediates, 6-chloro-4-hydrazino-1H-pyrazolo[3,4-d]pyrimidine 2 or oxypurinol 4, starting from 2,4,6-trichloropyrimidine-5-carbaldehyde 1. Their inhibitory activities against bovine milk xanthine oxidase in vitro are also described; i.e. the pyrazolotriazolopyrimidines 12 were several hundred times more potent than allopurinol.