Synthesis and antibacterial activity of 1H-pyrazolo[3,4-b]pyrazine and -pyridine derivatives.
The investigations of new pyrazine and pyridine derivatives showing an antibacterial activity have been made. Upon treatment of 3-chloro-2-cyanopyrazine [1] and 2-chloro-3-cyanopyridine with 1,1-dimethyl-hydrazine, 1-aminopiperidine and 1-amino-4-methylpiperazine, either the pyrazolo-pyrazine (1), and -pyridine (2) derivatives, or ammonium salts (3-8) were obtained, according to the reaction conditions. Compound 1 was obtained in the reaction of the initial nitrile with methylhydrazine as well. The reactions of 1 gave the following derivatives: acylation-(9), that with p-chlorobenzoic aldehyde-(10), and with phenyl-isothiocyanate-(11). 3-Chloro-2-cyanopyrazine treated with hydrazine hydrate gave amidrazone (12), which upon condensation with p-chlorobenzoic aldehyde produced (13). The compounds obtained were tested in vitro for their tuberculostatic activity. The minimal inhibitory concentration (MIC) values were within 22-100 microg/cm3. Compounds 1, 5 and 6 were also tested in vitro for their activity towards 25 strains of anaerobic, and 25 strains of aerobic bacteria. They appeared to be of elevated activity towards the anaerobes and of low one towards the aerobes (Table 2).
Foks
Henryk
H
Department of Organic Chemistry, Medical University of Gdańsk, 107, Al. Gen. J. Hallera, 80-416 Gdańsk, Poland. hfoks@amg.gda.pl
Pancechowska-Ksepko
Danuta
D
Kedzia
Anna
A
Zwolska
Zofia
Z
Janowiec
Mieczysław
M
Augustynowicz-Kopeć
Ewa
E
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D006089:Gram-Negative Anaerobic Bacteria / Q000187:drug effects; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D008956:Models, Chemical; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*
C478081:1H-pyrazolo(3,4-b)pyridine; D000900:Anti-Bacterial Agents; D011720:Pyrazoles; D011725:Pyridines; D008795:Metronidazole