Synthesis and in vitro anti-Mycobacterium activity of N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides. Preliminary toxicity and pharmacokinetic evaluation

Disseminated infections with Mycobacterium tuberculosis (MT) and Mycobacter ium avium complex (MAC) are increasingly opportunistic diseases in patients with advanced acquired human immunodeficiency syndrome (AIDS). A series of N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides has been synthesize d, and MICs for MT and MAC strains, either standard or isolated from infect ed patients, have been determined. Preliminary tests show a good activity a nd a very low toxicity for some derivatives. Pharmacokinetic studies in the rat show a very rapid elimination from the body after intravenous administ ration and a poor absorption after oral administration.