Metabolism of 3-acetamido-6-methyl-8-n-propyl-s-triazolo (4,3-a)pyrazine (I.C.I. 58,301) in animals.
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1. The metabolism and disposition of 14C-acetamidophenyl pyrazinone has been studied in rat, dog and cynomolgus monkey. The compound was well absorbed and rapidly excreted in urine and faeces by all three species. 2. Distribution of 14C-pyrazinone was rapid and extensive with the exception of the central nervous system where concentrations were at, or below, the limit of detection. 3. Whereas, in in vitro studies, metabolites (but not the parent compound) weakly inhibited some activities of the cytochrome P-450 system, there was evidence from in vivo studies in the rat that the compound and/or its metabolite(s) are weak selective inducers of cytochrome P-450. 4. Metabolite patterns were similar in all three species. The major route of metabolism was glucuronidation at the oxygen of the pyrazinone ring. Other metabolites originated from metabolism by gut microflora with subsequent hepatic metabolism.
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Hydrogenation of 4-N-substituted thiosemicarbazonic acid acetylpyrazine derivatives with NaBH4 in dry ethanol led to seventeen new compounds. The in vitro tuberculostatic activity investigations of the 15 synthesized compound were carried out. MIC few of i.v. compounds were lower than 32 micrograms/cm3.
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It was found that reaction of sodium alcoholates and cyanopyrazine yields alkoxypyrazine-nitriles. In heterogenic reaction both 2-alkylimidesters-6-chloropyrazine or 2-alkylimidoesters-6-alkoxypyrazine can be obtained dependent. This is dependent on quantity of alcohol used for reaction. Final products, alkoxypyrazinethioamides were tested for tuberculostatic activity (MIC within 31-500 mcg/cm3).