Studies on pyrazine derivatives--XXXIV. Synthesis and tuberculostatic activity of alpha-oxo ketene dithioacetals pyrazine derivatives.

The alpha-oxo ketene dithioacetalic derivatives (2a-e) were obtained by the reaction of 2-acetylpyrazine (1) with CS2 and appropriate mono- or dihalogeno-compound. An action of the primary amines and diamines upon 3,3-di(methylsulphanyl)-1-(2-pyrazinyl)-2-propen-1-one (2a) yielded 3-(alkylamino)-3-(methylsulphanyl)-1-(2-pyrazinyl)-2-propen-1-on e (3a-g), 1-(2-pyrazinyl)-2-tetrahydro-1H-2-imidazolyliden-1-ethanone (3h) and the 2-hexahydro-2-pyrimidinyliden-1-(2-pyrazinyl)-1-ethanone derivatives (3i-j), respectively. Tuberculostatic activity of the studied compounds was found to be low except the compound 2b (MIC 192-62 micrograms/cm3; MIC 210-31 micrograms/cm3).

Studies on pyrazine derivatives. XXXIII. Synthesis and tuberculostatic activity of 1-[1-(2-pyrazinyl)-ethyl]-4-N-substituted thiosemicarbazide derivatives.

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.

Studies on pyrazine derivatives. XXXII. Synthesis and tuberculostatic activity of acetylpyrazine thiosemicarbazone derivatives.

Syntheses of 4-N-substituted thiosemicarbazoic acetylpyrazine derivatives have been described. The in vitro microbiological investigations of the 25 synthesized compound were carried out.

[Investigations of pyrazine derivatives. Part XXVII. Synthesis and tuberculostatic activity of some 6-alkoxypyrazine-2-carbotioamids]. / Badania nad pochodnymi pirazyny. XXVII. Synteza i dzialanie tuberkulostatyczne 6-alkoksypirazyno-2-karbotioamidów.

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).

Reactions of cyanomethylbenzimidazoles. Part IV. Derivatives of 2-[alpha-cyano-beta-aryl-(dialkyl)-vinyl]-benzimidazole and N-arylthioamides of benzimidazolyl-2-alpha-cyanoacetic acid and their tuberculostatic activity.

Several derivatives of N-arylthioamide of benzimidazolyl-2-alpha-cyanoacetic acid and 2-(alpha-cyano-beta-chlorophenyl)-benzimidazole and its 4(7)- and 5(6)-methyl derivatives have been obtained. Tuberculostatic activity of these compounds was determined on the Mycobacterium tuberculosis H37Rv strain. LD50 values were determined for derivatives of 2-(alpha-cyano-beta-arylvinyl)-benzimidazoles. The compounds show moderate toxicity.

Studies on quantitative relationships between the structure and in vitro tuberculostatic potency of 2-cyanomethylbenzimidazole derivatives.

Quantitative relationships were studied between in vitro tuberculostatic potency and physico chemical parameters relating to the structure of 2-cyanomethylbenzimidazoles. The activity of the compounds was found to be mathematically described as a square function of molar refractivity of the substituent or the RM values and a linear function of the wavelength at the absorption maximum or the connectivity index for the aromatic ring in the substituent. The equation was obtained, statistically significant on the 99% level and describing of about 83% of variance in activity data, which may be of value for the design of new active derivatives.

Reactions of cyanomethylbenzimidazoles. Part III. Reaction of cyanomethylbenzimidazoles with isocyanates and isothiocyanates.

In the reaction of 2-cyanomethylbenzmidazole and their 1- and 5-methyl derivatives with aromatic isocyanates and isothiocyanates, 23 N-arylamides resp. thioamides of benzimidazolyl-2-alpha-cyanoacetic acid were obtained. The structure of the newly compounds (Table 1) was confirmed by NMR and IR spectra. Some of these shown moderate tuberculostatic activity in vitro.

Reactions of cyanomethylbenzimidazoles. Part II. Reaction of cyanomethylbenzimidazoles with aldehydes methylketones and nitroso compounds.

Position of CH2CN group in the benzimidazole system determines the activity of hydrogen atoms of CH2 group in condensation reactions. Some of the obtained compounds show high tuberculostatic activity.