Studies on Pyrazine Derivatives, XLIV: Synthesis and Tuberculostatic Activity of 4-Substituted 3,4,5,6-Tetrahydro-2H-[1,2′]-Bis-Pyrazine Derivatives

Abstract

2-chloro-3-cyanopyrazine was a substrate in the syntheses of some potentially tuberculostatic pyrazine derivatives. This compound, upon action of secondary amines, pyrazine derivatives 1-phenyl-, 1-piperonyl-, 1-(4-fluorophenyl)-, 1-(2-pyridil)-, and 1-benzylpiperazine, gave the corresponding nitriles ( 1a–e ). Compounds 1c , d , e were changed into the amidoximes ( 2c , d , e ) by hydroxylamine action. Derivatives 1a–e were transformed into the corresponding thioamides ( 3a–e ) when treated with ammonium polysulphide. Two of these, thioamides, 3a and 3b , in the cyclization reactions with ethylenediamine gave the imidazolines ( 4a , b ) with phenacyl bromide—the thiazole derivatives ( 5a , b ). The compounds obtained were tested in vitro for their tuberculostatic activity. The tuberculostatic activity of compound 5b was the highest: MIC 3.1–7.8 μ g/mL.