Facile synthesis and antiproliferative activity of new 3-cyanopyridines

Abstract

BackgroundPyridines have been reported to possess various pharmacological activities.ResultsSodium 3-oxo-3-(2-oxo-2H-chromen-3-yl)prop-1-en-1-olate (2) and sodium 3-oxo-3-(3-oxo-3H-benzo[f]chromen-2-yl)prop-1-en-1-olate (7) were prepared and reacted with 2-cyano-N’-(1-aryl(heteryl)ethylidene)acetohydrazides 3a–d to produce 2-oxo-1,2-dihydropyridine-3-carbonitrile derivatives 5a–d and 9a–d, respectively, in good yields. Also, 3a–d reacted with sodium (2-oxocyclopentylidene)methanolate (11a) or sodium (2-oxocyclohexylidene) methanolate (11b) to yield 2-oxo-tetrahydro-1H-cyclopenta[b]pyridine-3-carbonitriles 13a–d and 2-oxo-hexahydroquinoline-3-carbonitriles 13e–h, respectively. The mechanisms that account for the formation of the products are discussed. Additionally, the structures of all the newly synthesized products are confirmed, based on elemental analysis and spectral data. Several of the newly synthesized compounds are evaluated for their antitumor activity against HEPG2 and their structure activity relationship (SAR) was studied.ConclusionsThe results revealed that the pyridine derivatives 5c and 5d (IC50 = 1.46, 7.08 µM, respectively) have promising antitumor activity against liver carcinoma cell line (HEPG2), compared to the reference drug, doxorubicin.

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

“…Heterocyclic scaffolds have attracted considerable attention in the design of many biologically active synthetic compounds [ 10 , 11 , 12 , 13 , 14 ]. Pyrimidine, six-membered ring heterocyclic ring with two nitrogen atoms, is widely present in several natural and synthetic drugs [ 15 ].…”

Synthesis and characterization of some new pyridines, thieno[2,3‐b] pyridines and pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐4(3H)‐ones bearing styryl moiety

“…Functionally substituted‐pyridines are bioactive small molecules possess a wide range of applications . Accordingly, a number of powerful synthetic strategies have been developed to effectively access this heterocyclic family .…”

Synthesis and antitumor evaluation of some new thiazolopyridine, nicotinonitrile, pyrazolopyridine, and polyhydroquinoline derivatives using ceric ammonium nitrate as a green catalyst

“…[ 20 ] Polysubstituted pyridine containing cyano group exhibited antitumor activity in numerous publications. [ 21–27 ] In addition, cyano pyridine derivatives have shown to possess promising anti‐microbial, [ 28–30 ] antioxidant, [ 31–33 ] antibiotic, [ 34–36 ] anti‐inflammatory, [ 37,38 ] analgesic, [ 39 ] anti‐convulsant, [ 40 ] and anticancer activities. [ 41 ] Also, pyridine is widely distributed in many biological molecules, and found in drugs such as nifedipine.…”