Pyranopyridine Derivatives Research Articles

Efficient synthesis of pyrano[2,3-b]pyridine derivatives using microwave or solar energy

Pyranopyridine derivatives are an important class of heterocyclic compounds due to their biological activities such as antitumor and antibacterial. However, conventional procedures for their synthesis produce large amounts of toxic by-products. Therefore, there is a need to develop simple, efficient and environmentally benign procedures. Here, a one-pot multicomponent protocol is designed for the synthesis of pyrano[2,3-b]pyridone derivatives by reaction of equimolar amounts of 6-hydroxy-1,4-dimethyl-1,2-dihydropyridines, aryl aldehydes and malononitrile, using both microwave heating and solar thermal energy in aqueous EtOH (50%) in the presence of a catalytic amount of K2CO3. The products were obtained in 84–90% yields in 10–20 min by microwave heating, and in 90–96% yields in 2–3 h using solar energy.

Cytotoxicity, oxidative stress, and apoptosis in K562 leukemia cells induced by an active compound from pyrano-pyridine derivatives.

Recent studies have reported the potential of pyrano-pyridine compounds in inhibiting cell growth and apoptosis induction in cancer cells. Here, we investigated the effect of new pyrano-pyridine derivatives on proliferation, oxidative damages, and apoptosis in K562 leukemia cells. Among different tested compounds, we found 8-(4-chlorobenzylidene)-2-amino-4-(4-chlorophenyl)-5, 6, 7, 8-tetrahydro-6-phenethyl-4H-pyrano-[3,2-c]pyridine-3-carbonitrile (4-CP.P) as the most effective compound with IC50 value of 20 μM. Gel electrophoresis, fluorescence microscopy, and flow cytometry analyses indicated the apoptosis induction ability of 4-CP.P in K562 cells. Further analyses revealed that 4-CP.P induces significant increase in cellular reactive oxygen species production, lipid peroxidation, protein oxidation, and total thiol depletion. Interestingly, while 4-CP.P significantly increased the activity of superoxide dismutase, it reduced the catalase activity in a time-dependent manner. These data propose that 4-CP.P treatment causes free radicals accumulation that ultimately leads to oxidative stress condition and apoptosis induction. Therefore, we report the 4-CP.P as a novel, potent compound as a chemotherapeutic agent in cancer treatment.

Synthesis and anticancer activity of novel 2-substituted pyranopyridine derivatives

A novel series of 2-aminopyranopyridine derivatives (3–19) were synthesized utilizing 2-chloro-4-(thiophen-2-yl)-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carbonitrile (2) as a key starting compound. The structures of the newly synthesized compounds were confirmed on the basis of elemental analyses and infrared (IR), 1H, 13C-nuclear magnetic resonance (NMR) and mass spectra. Anticancer evaluation was carried out for the new derivatives against Hep-G2 (human liver carcinoma), MCF-7 (human breast carcinoma), Caco-2 (human colorectal adenocarcinoma) and HCT116 (human colorectal carcinoma) cell lines using doxorubicin as a reference drug. The biological results revealed that the compounds 12 and 14 exhibited more potent anticancer activity than the reference drug.

Molecular basis for inhibition of AcrB multidrug efflux pump by novel and powerful pyranopyridine derivatives

The Escherichia coli AcrAB-TolC efflux pump is the archetype of the resistance nodulation cell division (RND) exporters from Gram-negative bacteria. Overexpression of RND-type efflux pumps is a major factor in multidrug resistance (MDR), which makes these pumps important antibacterial drug discovery targets. We have recently developed novel pyranopyridine-based inhibitors of AcrB, which are orders of magnitude more powerful than the previously known inhibitors. However, further development of such inhibitors has been hindered by the lack of structural information for rational drug design. Although only the soluble, periplasmic part of AcrB binds and exports the ligands, the presence of the membrane-embedded domain in AcrB and its polyspecific binding behavior have made cocrystallization with drugs challenging. To overcome this obstacle, we have engineered and produced a soluble version of AcrB [AcrB periplasmic domain (AcrBper)], which is highly congruent in structure with the periplasmic part of the full-length protein, and is capable of binding substrates and potent inhibitors. Here, we describe the molecular basis for pyranopyridine-based inhibition of AcrB using a combination of cellular, X-ray crystallographic, and molecular dynamics (MD) simulations studies. The pyranopyridines bind within a phenylalanine-rich cage that branches from the deep binding pocket of AcrB, where they form extensive hydrophobic interactions. Moreover, the increasing potency of improved inhibitors correlates with the formation of a delicate protein- and water-mediated hydrogen bond network. These detailed insights provide a molecular platform for the development of novel combinational therapies using efflux pump inhibitors for combating multidrug resistant Gram-negative pathogens.

Synthesis and biological evaluation of new pyranopyridine derivatives catalyzed by guanidinium chloride-functionalized γ-Fe2O3/HAp magnetic nanoparticles

Herein, we described the synthesis of γ-Fe2O3@HAP-GndCl MNPs as an efficient and recyclable nanocatalyst for synthesis of new pyranopyridine derivatives under solvent-free condition and then evaluated for theirs antioxidant and antifungal activities.

ChemInform Abstract: Microwave‐Promoted, Metal‐ and Catalyst‐Free Decarboxylative α,β‐Difunctionlization of Secondary α‐Amino Acids via Pseudo‐Four‐Component Reactions.

AbstractAmino acids (III) and (VIII) react with 1,3‐diketones and two equivalents of aromatic aldehydes to give pyranopyrrole and pyranopyridine derivatives, respectively.

One-pot synthesis of new series of pyranopyridine derivatives using 3-cyano-6-hydroxy-4-methyl-pyridin-2(1H)-one as a novel nucleophile

Cyano-6-hydroxy-4-methyl-pyridin-2(1H)- one has been found as a useful synthetic precursor for a variety of pyranopyridine derivatives. We report here the one-pot three-component reactions of this compound with aromatic aldehydes and malononitrile using triethylamine as the catalyst in ethanol under refluxing condition to obtain highly functionalized 2-amino-4-aryl-7,8-dihydro- 5-methyl-4H-pyrano(2,3-b)pyridin-7-one-3,6-dicarbonitrile derivatives. High yields, low reaction times, use of non- toxic and inexpensive catalyst, and easy work-up are the main merits of this protocol. Graphical Abstract Keywords 3-Cyano-6-hydroxy-4-methyl-pyridin- 2(1H)-one · 2-Amino-4-aryl-7,8-dihydro-5-methyl- 4H-pyrano(2,3-b)pyridin-7-one-3,6-dicarbonitrile · Triethylamine

Direct, Facile, Eco-Friendly, and Four-Component Synthesis of Pyranopyridine Derivatives

The Bis[N-(3,5-dicumylsalicylidene)-anthracylaminato]zircon– ium(IV) dichloride efficiently catalyzed a one-pot four-component reaction of resorcinol, malononitrile, aromatic aldehydes, and cyclohexanone under solvent-free condition using ultrasonic irradiation to synthesize pyrano[2,3-b]pyridine derivatives in good to excellent yields.

ChemInform Abstract: Activated Anilide in Heterocyclic Synthesis: Synthesis of New Hydrazo, Dihydropyridazine, Tetrahydropyridine, Dihydropyridine and Pyranopyridine Derivatives.

AbstractTitle compounds with expected biological activities are synthesized starting from propanamide (III) or enaminonitrile (XII), respectively.

Activated anilide in heterocyclic synthesis: Synthesis of new hydrazo, dihydropyridazine, tetrahydropyridine, dihydropyridine and pyranopyridine derivatives

A series of new hydrazo, dihydropyridazine, tetrahydropyridine, dihydropyridine and pyranopyridine derivatives with known biological activity have been prepared through the reactions of 3-oxo-3-phenyl-N-(pyridine-3-yl) propanamide 3 and enaminonitrile 17 with some electrophilic reagents, nucleophilic reagents, and aryl diazonium salts. The newly synthesized compounds were characterized by IR, 1H NMR and mass spectral studies. A series of new hydrazo, dihydropyridazine, tetrahydropyridine, dihydropyridine and pyranopyridine derivatives with known biological activity have been prepared through the reactions of 3-oxo-3-phenyl-N-(pyridine-3-yl) propanamide 3 and enaminonitrile 17 with some electrophilic reagents, nucleophilic reagents, and aryl diazonium salts.

Bis(imino)pyridine (BIMP) Fe(II) catalyses one-pot green condensation of resorcinol, malononitrile, aromatic aldehydes and cyclohexanone

A novel, efficient and green approach for the synthesis of pyranopyridine derivatives through one-pot, four-component reaction of resorcinol, malononitrile, aromatic aldehydes and cyclohexanone using bis(imino)pyridine (BIMP) Fe(II) catalyst under solvent-free and ultrasonic irradiation is described. A rapid, green and efficient synthesis of 11-amino-8,9,10,12-tetrahydro-12-aryl-7H-chromeno[2,3-b]quinolin-1-ol derivatives through a multicomponent cyclocondensation of resorcinol, malononitrile, aromatic aldehydes and cyclohexanone in the presence of (4-nitro-2,6-diacetylpyridinebis(2,4,6-trimethylanil)) FeCl2 under ultrasonic irradiation has been described.

An expeditious synthesis of novel pyranopyridine derivatives involving chromenes under controlled microwave irradiation

An efficient synthesis of novel pyrano[2,3-b]pyridine derivatives has been achieved by the cyclocondensation of 2-amino-3-cyano-4H-chromenes and cyclohexanone in the presence of aluminium chloride under controlled microwave irradiation. The experimental conditions have been thoroughly optimized and established, allowing significant rate enhancements and excellent yields. The starting 4H-chromenes were obtained using one pot DBU-catalysed microwave induced multicomponent condensation of resorcinol, malononitrile and aromatic aldehydes.

ChemInform Abstract: Novel Pyranopyridine Derivatives from an Enaminone.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Novel pyranopyridine derivatives from an enaminone

AbstractThe pyranopyridine derivatives 2 and 15B were synthesized from enaminone 1 and hydroxylamine in the presence of 2N and 1N aqueous sodium hydroxide solutions, and consecutive reactions with these compounds are described.

Reactions of six-membered heterocyclic β-enaminonitriles with electrophilic reagents

The nitriles I reacted with acetylacetone and with ethyl acetoacetate to afford 2-amino-3-cyano-4H-pyran derivatives. They reacted further to yield pyranopyridine derivatives. The reaction of V with acetylacetone afforded the pyridinethione VIII. This afforded, reacting with aromatic aldehydes or with cinnamonitriles quinoline derivatives XVII.