Derivatives of p-aminobenzoic acid and their action on the growth of bacteria
SummaryVarious derivatives of P.A.B. obtained by introduction of substituents in the benzene-nucleus have been examined for their action on the growth ofAerobacter aerogenes in a simple synthetic medium and ofDiplococcus pneumoniae in ascites-broth without peptone.The following results have been obtained:1.The 2-amino, 3-amino, 3-chloro, 3-bromo, 2-methyl, 3-methyl, and 2.3-dimethyl derivatives of P.A.B., and also 2-sulfanilamido-4-aminobenzoic acid have sulfonamide activity.2.The 2-hydroxy, 2-fluoro, and 2-nitro derivatives have an antisulfonamide activity similar to the activity of P.A.B., although weaker.3.The 3-hydroxy, 2-chloro, and 2-bromo derivatives show sulfonamide-activity in relatively high concentrations. In lower concentrations they act as anti-sulfonamides.4.The 3-nitro, 2.6-dimethyl, and 3.5-dimethyl derivatives, and methyl 2-acetamino-4-amino-benzoate are completely inactive. These results have been compared with those of other investigators and the causes of some contradictions have been elucidated.
Dérivés simples de l'acide p-aminobenzoïque agissant comme sulfonamides et antisulfonamides
RésuméPour plusieurs dérivés de l'acide p-aminobenzoïque, substitués dans le noyau, on a examiné l'activité sulfonamide ou anti-sulfonamide sur des pneumocoques “in vitro”.Les acides 2,4-diamino- et 3,4-diamino-benzoïques exercent la même action bactériostatique que la sulfanilamide. Les acides 2-chloro- et 2-bromo-4-aminobenzoïques empêchent l'action inhibitrice de la sulfanilamide. Quelques autres dérivés ne présentent nulle activité.
Pharmacokinetics and Metabolism of 14C-Brivaracetam, a Novel SV2A Ligand, in Healthy Subjects
This study was designed to investigate the human absorption, disposition, and mass balance of 14C-brivaracetam, a novel high affinity SV2A ligand with potent anticonvulsant activity. Six healthy male subjects received a single p.o. dose of 14C-brivaracetam (150 mg, 82 μCi, or 3.03 MBq). Serial blood and complete urine and feces were collected until 144 h postdose. Expired air samples were obtained until 24 h. Brivaracetam was rapidly absorbed, with Cmax of 4 μg/ml occurring within 1.5 h of dosing. Unchanged brivaracetam amounted to 90% of the total plasma radioactivity, suggesting a modest first-pass effect. Plasma protein binding of radioactivity was low (17.5%). Urinary excretion exceeded 90% after 2 days, and the final mass balance reached 96.8% of the radioactivity in urine and 0.7% in feces. Only 8.6% of the radioactive dose was recovered in urine as unchanged brivaracetam, the remainder being identified as non–cytochrome P450 (P450)- and P450-dependent biotransformation products resulting from hydrolysis of the amide moiety (M9, 34.2%), hydroxylation of the n-propyl side chain (M1b, 15.9%), and a combination of these two pathways leading to the hydroxy acid (M4b, 15.2%). Minor amounts of taurine and glucuronic acid conjugates and other oxidized derivatives were also identified. Brivaracetam is completely absorbed, is weakly bound to plasma proteins, extensively biotransformed through several metabolic pathways, and eliminated renally.