Date of Award

1-1-1983

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Abstract

A total of 21 various 5-aryl-2H-tetrazoles, 5-aryl-2H-tetrazole-2-acetic acids, and (4-phenyl-5-aryl-4H-1,2,4-triazole-3-yl)thioacetic acids were synthesized and tested as possible antiinflammatory agents. The aryl substituent consisted of a substituted phenyl group with the following substitution: H, 4-OMe, 3,4-diOMe, 3,4,5-tri-OMe, 4-OH, 3,4,-di-OH, or 3,4,5-tri-OH. All compounds and intermediates were characterized on the basis of their infrared and proton magnetic resonance spectral data. Satisfactory elemental analysis were obtained for all novel compounds.All 5-aryl-2H-tetrazoles, 5-aryl-2H-tetrazole-2-acetic acids, and (4-phenyl-5-aryl-4H-1,2,4-triazole-3-yl)thioacetic acids were examined for superoxide scavenging ability in an in vitro assay. The compounds tested were assayed at 1 x 10('-4)M; the most active compounds were assayed at two lesser concentrations. No multi-phasic responses were found. Analysis of the in vitro data indicated the order of superoxide scavenging activity was 3,4,5-tri-OH > 3,4-di-OH > 4-OH > 3,4,5-tri-OMe = 3, 4-di-OMe = 4-OMe = H.The three trihydroxy compounds were tested for antiinflammatory activity in vivo in the carrageenan-induced rat paw edema reaction and the reverse passive Arthus reaction under the direction of Dr. Ivan Otterness of Pfizer Pharmaceuticals (Gronton, CT). 5-(3,4,5-Trihydroxyphenyl-2H-tetrazole, 5-(3,4,5-trihydroxyphenyl)-2H-tetrazole-2-acetic acid, and (4-phenyl-5-(3,4,5-trihydroxyphenyl)-4H-1,2,4-triazole-3-yl)thioacetic acid were found to be inactive in these in vivo tests.

Download

Share

COinS