Therapy for urolithiasis by hydroxamic acids. II. Urease inhibitory potency and urinary excretion rate of hippurohydroxamic acid derivatives.

Publisher Website
Google Scholar
Abstract
The apparent I50 [median inhibitory concentration] values of various hippurohydroxamic acids against urease activity of sword bean were mostly 0.5-2.0 .mu.M regardless of hydrophobicity of their substituents. The marked increase of hydrophilicity caused by substitution of trimethoxy groups conspicuously decreased the inhibitory potency. Methylation at .alpha.-position of the hydroxamic acid group in these compounds remarkably decreased the inhibitory potency, probably owing to steric hindrance by the .alpha.-methyl group. Thenoyl-, furoyl- and nicotinoglycinohydroxamic acids which are bioisostereomers of hippurohydroxamic acid had I50 values of 0.64, 1.3 and 5.3 .mu.M, respectively. The inhibitory potency of some substituted hippurohydroxamic acids against the ureolytic activity of intact Proteus mirabilis isolated from patients with urinary tract infection, were 1/2 to 1/10 of those against urease activity of sword bean. The m- and p-nitro-, m- and p-methoxy-, m- and p-acetylaminohippurohydroxamic acids and furoylglycinohydroxamic acids showed high urinary excretion rates of 14-16% of the doses administered orally to rats, while most of the others had excretion rates of .apprx. 3-5%.