4-Trifluoromethylimidazoles and 5-(4-pyridyl)-1,2,4-triazoles, new classes of xanthine oxidase inhibitors

The syntheses of a number of 2-substituted 4-trifluoromethylimidazoles and 3-substituted 5-(4-pyridyl)-1,2,4-triazoles are described. The trifluoromethylimidazoles were prepared from 3,3-dibromo-1,1,1-trifluoroacetone after hydrolysis with aqueous sodium acetate solution and condensation with an ald...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1975-09, Vol.18 (9), p.895-900
Main Authors: Baldwin, J. J, Kasinger, P. A, Novello, F. C, Sprague, J. M, Duggan, D. E
Format: Article
Language:English
Subjects:
Animals
Cattle
Imidazoles - chemical synthesis
Imidazoles - pharmacology
Kinetics
Pyridines - chemical synthesis
Pyridines - pharmacology
Structure-Activity Relationship
Triazoles - chemical synthesis
Triazoles - pharmacology
Xanthine Oxidase - antagonists & inhibitors
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Summary:The syntheses of a number of 2-substituted 4-trifluoromethylimidazoles and 3-substituted 5-(4-pyridyl)-1,2,4-triazoles are described. The trifluoromethylimidazoles were prepared from 3,3-dibromo-1,1,1-trifluoroacetone after hydrolysis with aqueous sodium acetate solution and condensation with an aldehyde in the presence of ammonia. Basic hydrolysis of the trifluoromethyl group was found to provide a facile method for the synthesis of imidazole-4-carboxylic acids. In the imidazole series a 2-aryl substituent and a free imino group were required for xanthine oxidase inhibitory activity. The triazoles were obtained through the reaction of an aroylhydrazine and an imino ether followed by thermal ring closure of the intermediate acylamidrazone. As in the imidazole series, a free imino group is an absolute requirement for in vitro activity. Additional structure-activity relationships of these compounds are presented.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00243a007