| Abstract [eng] |
Fused ring systems that contain pyrazole are mostly applied in pharmacy because they exhibit a broad spectrum of biological activities, such as anticancer, antioxidant, antibacterial, antiviral, antifungal, antitubercular, antiosteoarthritic, antidiabetic, anti-inflammatory, antipyretic, anticonvulsant, antiparasitic and vasodilatory. Derivatives containing pyrazole ring are also of great interest due to their applicability in dye, agriculture industries and material science. The aim of this work was to develop a synthetic route to the condensed pyrazolo[4,3-c]pyridine derivatives starting from 1-phenyl-3-pyrazolidinone and to explore their biological activity. The starting 1-phenyl-3-pyrazolidinone was first converted into 3-hydroxy-1-phenyl-1H-pyrazolo-4-carbaldehyde following oxidation, alkylation and formylation reactions, respectively. The obtained compound was then used as precursor to synthesize 4-formyl-1-phenyl-1H-pyrazol-3-yl trifluoromethanesulphonate which was converted into 3-(hex-1-in-1-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde and 1-phenyl-3-(phenylethynyl)-1H-pyrazole-4-carbaldehyde under Sonogashira reaction conditions. Pyrazolo[4,3-c]pyridine systems were obtained by a three-step procedure. First, 3-(hex-1-in-1-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde and 1-phenyl-3-(phenylethynyl)-1H-pyrazole-4-carbaldehyde were treated with Gringnard reagents to afford alcohols which then were transformed into azide-alkynes. The formation of 7-iodo-4-methyl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine and 6-butyl-7-iodo-4-isopropyl-2-phenyl-2H-pyrazolo[4,3-c]pyridine was obtained via electrophilic cyclization reaction of azide-alkynes. In order to synthesize more various pyrazolo[4,3-c]pyridine derivatives Suzuki-Miyaura, Heck and Buchwald-Hartwig Pd-catalyzed cross-coupling reactions were employed. Evaluation of anticancer activity against myelogenous leukemia and breast adenocarcinoma cells showed that the most active compounds possess methyl and phenyl groups at fourth and sixth positions and amino, 4-trifluoromethylphenyl, 4-methoxyphenyl and iodo − at seventh. The structures of products were confirmed by data of NMR, IR spectroscopy, mass spectrometry and elemental analysis. Biological evaluation was carried out by standard “Calcein AM” method. |
