Etude pharmacologique d’un nouveau composé analgésique antiinflammatoire, la Glaphénine

Biotransformations of glafenine in the rat and in man

“…The slightly greater excretion of the N-oxide V recorded after injection of II instead of I indicated that 1 Allais, A. and Girault, P. -Unpublished data.…”

“…Minor differences were encountered only in the case of hydroxyglafenine III which was Table 3 Characterization of glafenine metabolites excreted in human urine by reverse isotope dilution a) See table l. b) Specific activity expressed as d.p.m.pg-l After addition of radioinert compounds, urine samples were extracted before hydrolysis (V) or after enzyme hydrolysis (III) or alkalinization (II and IV). Table 4 Urinary excretion of total radioactivity, of glafenine and of its metabolites after oral administration of 5 mg.kg-f of 14C_I in rat and man Rat Man Expressed as % of dose before (1) and after (2) enzyme hydrolysis. Urine was collected from 4 rats for 6 hrs and from a man for 4 hrs after administration.…”

Synthesis and antibacterial activity of 2'-substituted chelocardin analogs

“…J Cl: caled, 6.51; found, 5.99. (a) 4-Methylpiperazinoiminochelocardin Dihydrochloride (9). A solution of l-amino-4-methylpiperazine dihydrochloride (2.62 g, 12.8 mM) in 100 mL of methanol was added to chelocardin free base (5 g, 12.2 mM) suspended in 200 mL of methanol.…”

“…In vivo, they are converted to chelocardin at widely varying rates; some of them are excreted unchanged in the urine. To determine whether these derivatives have intrinsic activity, bacterial growth inhibition studies of Proteus vulgaris using the p-chloroanilino (35) and the 4-methylpiperazinoimino (9) derivatives were performed. Inhibition curves for chelocardin (1) hydrochloride and compounds 35 and 9 shown in Figures 1-3 indicated no time lag in the inhibition effect after addition of antibiotics.…”

“…To determine whether these derivatives have intrinsic activity, bacterial growth inhibition studies of Proteus vulgaris using the p-chloroanilino (35) and the 4-methylpiperazinoimino (9) derivatives were performed. Inhibition curves for chelocardin (1) hydrochloride and compounds 35 and 9 shown in Figures 1-3 indicated no time lag in the inhibition effect after addition of antibiotics. Since the derivatives are quite resistant to ordinary chemical hydrolysis and the enzymatic in vivo hydrolysis in rats, monkeys, and mice is relatively slow, the results indicate that the derivatives do have intrinsic activity.…”