New N-Alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides as Antituberculous Agents with Improved Pharmacokinetics.
2003
Infections caused by multidrug-resistant Mycobacterium tuberculosis (MT) and non-tuberculous mycobacteria are difficult to treat and, indeed, new therapeutic agents are being sought. As a part of an ongoing research in our laboratories, novel N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides have been synthesized and evaluated against several strains of MT and Mycobacterium avium complex (MAC). The pharmacokinetics and relative bioavailability after intravenous administration of three derivatives have been investigated. Introduction of a hydroxyl or a tertiary amino group in the N-alkyl chain resulted in an improved pharmacokinetic profile without affecting sensitively the antituberculous potency.
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