Individual synthetic dithiocarbamate derivatives have promising antileprosy activity.

A series of substituted 2-nitro-1-(4-tolylsulfonyl)-2-(3-methylphenyl-1,2,4-oxadiazol-5-yl)ethanes were synthesized and their antimycobacterial activity with respect to Mycobacterium Lufu and Mycobacterium tuberculosis species was studied.The well-known antituberculous drugs are widely used in clinical practice, but their high toxicity and the appearance of drug-resistant strains [1, 2] stimulate both the modification of the existing substances and the search for new agents possessing antimycobacterial activity. In the search for new compounds possessing this type of activity at a low toxicity, we have synthesized a series of previously unreported substituted 2-nitro-1-(4-tolylsulfonyl)-2-(3-methylphenyl-1,2,4-oxadiazol-5-yl)ethanes (IIa -IIh) and characterized these compounds with respect to their antimycobacterial activity. The target compounds II were obtained via sulfonylation of the corresponding substituted 2-nitro-1-chloro-2-(3-methylphenyl-1,2,4-oxadiazol-5-yl)ethanes (Ia -Ih) [3,4] with sodium 4-tolylsulfinate [5] on heating (50°C) in ethanol. The yields and characteristics of the synthesized compounds are listed in Table 1.

A series of carbamate derivatives of 1,2-oxazine was obtained by means of [2 + 4]-cycloaddition of 1,3-dienes to C-nitroso-alkyl-N-arylcarbamates. The antimycobacterial activity of the synthesized compounds with respect to Mycobacterium tuberculosis and Mycobacterium lufu species was studied in vitro in comparison to isoniazid and dapsone. The activity of the newly synthesized compounds significantly depends on the nature and position of substituents in the oxazine nucleus and weakly depends on the nature of substituents in the carbamate moiety. Among the compounds tested, the maximum antimycobacterial activity was observed for 4,5-dimethyl-2-( p-methoxycarbonylamino)phenyl-3,6-dihydro-1,2-oxazine.

Effects of some dialkyldithiocarbamate derivatives on multiplication of M. leprae were studied in infected mice. Compounds significantly suppressing M. leprae proliferation were selected. By antibacterial activity one of these compounds was superior to dapsone, the main antileprosy drug.

Azo compounds Q 0160Synthesis and Antimycobacterial Activity of Triazene Derivatives of N-Arylcarbamates. -It is shown that modification of the isonicotinic hydrazides to triazene derivatives of N-arylcarbamates (III) does not result in an essential decrease of activity against Mycobacterium tuberculosis and Mycobacterium lufu as compared to isoniacid and dapsone. -(VELIKORODOV, A. V.; URLYAPOVA, N. G.; DAUDOVA, A. D.; Khim.-Farm. Zh. 39 (2005) 3, 16-17; Astrakhan State Univ., Astrakhan 414056, Russia; Russ., Abstr. Eng.) -Mischke 32-090