Synthesis of Some New [1,8]Naphthyridine,Pyrido[2,3‐d]‐Pyrimidine,and Other Annulated Pyridine Derivatives

2‐Aminopyridine‐3‐carbonitrile derivative 1 reacted with each of malononitrile, ethyl cyanacetate, benzylidenemalononitrile, diethyl malonate, and ethyl acetoacetate to give the corresponding [1,8]naphthyridine derivatives 3 , 5 , 8 , 11 , and 14 , respectively. Further annulations of 3 , 5 , and 8 gave the corresponding pyrido[2,3‐b][1,8]naphthyridine‐3‐carbonitrile derivative 17 , pyrido[2,3‐h][1,6]naphthyridine‐3‐carbonitrile derivatives 18 and 19 , respectively. The reaction of 1 with formic acid, formamide, acetic anhydride, urea or thiourea, and 4‐isothiocyanatobenzenesulfonamide gave the pyridopyrimidine derivatives 20a , b , 21 , 22a , b , and 26 , respectively. Treatment of compound 1 with sulfuric acid afforded the amide derivative 27 . Compound 27 reacted with 4‐chlorobenzaldehyde and 1H‐indene‐1,3(2H)‐dione to give the pyridopyrimidine derivative 28 and spiro derivative 30 , respectively. In addition, compound 1 reacted with halo compounds afforded the pyrrolopyridine derivatives 32 and 34 . Finally, treatment of 1 with hydrazine hydrate gave the pyrazolopyridine derivative 35 . The structures of the newly synthesized compounds were established by elemental and spectral data.     

Synthesis and Evaluation of Pyrido[2,3‐d]pyrimidine and 1,8‐Naphthyridine Derivatives as Potential Antitumor Agents

New series of pyrido[2,3‐d]pyrimidine and 1,8‐naphthyridine derivatives were synthesized from 2‐amino‐6‐(phenoxathiin‐2‐yl)‐4‐(thiophene‐2‐yl) nicotinonitrile as starting material, and their structures were characterized on the basis of the spectral data. Most of the synthesized compounds were evaluated for their cytotoxic activity against two cancer cell lines, namely, breast cancer Michigan Cancer Foundation‐7 (MCF‐7) and prostate cancer human prostatic carcinoma cell line (PC‐3) using MTT assay. Some of these compounds showed potent cytotoxic effect concluded from their IC₅₀ values.     

Synthesis and characterization of new complexes of the type [Ru(CO)2Cl2 (2‐phenyl‐1,8‐naphthyridine‐kN) (2‐phenyl‐1,8‐naphthyridine‐kN′)]. Preliminary applications in homogeneous catalysis

Novel ruthenium (II) complexes were prepared containing 2‐phenyl‐1,8‐naphthyridine derivatives. The coordination modes of these ligands were modified by addition of coordinating solvents such as water into the ethanolic reaction media. Under these conditions 1,8‐naphthyridine (napy) moieties act as monodentade ligands forming unusual [Ru(CO)₂Cl₂(η¹‐2‐phenyl‐1,8‐naphthyridine‐ kN )(η¹‐2‐phenyl‐1,8‐naphthyridine‐kN′)] complexes. The reaction was reproducible when different 2‐phenyl‐1,8‐naphthyridine derivatives were used. On the other hand, when dry ethanol was used as the solvent we obtained complexes with napy moieties acting as a chelating ligand. The structures proposed for these complexes were supported by NMR spectra, and the presence of two ligands in the [Ru(CO)₂Cl₂(η¹‐2‐phenyl‐1,8‐naphthyridine‐ kN )(η¹‐2‐phenyl‐1,8‐naphthyridine‐kN′)] type complexes was confirmed using elemental analysis. All complexes were tested as catalysts in the hydroformylation of styrene showing moderate activity in N,N′‐dimethylformamide. Copyright © 2008 John Wiley & Sons, Ltd.     

Reactions of Naphthyridines with Aldehydes: Novel Derivatives with Red‐Fluorescence Emissions and Two‐Photon Absorptions

Four new 1,8‐naphthyridine derivatives were synthesized by reacting the parent molecules with aldehydes and characterized. Two of the compounds have completely new and unusual skeletons, and display red‐fluorescence emissions and two‐photon absorption. Their structures were determined using MS, 1D and 2D NMR, and density functional theory calculations. The structural investigations of 2‐methyl‐1,8‐naphthyridine hydrochloride and hydrobromide showed that abundant hydrogen‐bonds and π‐ π interactions lead to extended networks.     

Synthesis and biological effects of new derivatives of benzotriazole as antimicrobial and antifungal agents

Derivatives of 2‐aminothiophene‐3‐carbonitrile, 2‐thioxopyridine‐3‐carbonitrile, 1,8‐naphthyridine‐2‐one, thieno[2,3‐b]pyridine‐5‐carbonitrile and thieno[2,3‐d]pyrimidine incorporating with a 1H‐benzo‐triazole moiety or 1,3,4‐thiadiazole derivatives incorporating with a benzotriazol‐1‐ylmethyl group have been synthesized and tested for antimicrobial and antifungal activities. The structures of the newly synthesized compounds have been established on the basis of their analytical and spectral data.     

Synthesis of substituted pyrimido[4,5‐b] and [5,4‐c]‐[1,8]naphthyridines

Ethyl 1‐ethyl‐7‐methyl‐4‐oxo‐1,4‐dihydro[1,8]naphthyridine‐3‐carboxylate ( 1 ), precursor of nalidixic acid, has been converted in two steps through ([1,8]naphthyridin‐3‐yl)carbonylguanidine derivatives into substituted pyrimido[4,5‐b] and [5,4‐c][1,8]naphthyridines.     

The Use of 2‐Chloro‐4H‐4‐oxo‐pyrido[1,2‐a]pyrimidine as a Building Block in the Synthesis of Some New Heterocyclic Compounds

New approaches for the synthesis of some heterocyclic compounds, such as the pyridopyrimidodiazepine derivative 3 , pyrazolopyrido[1,2‐a]pyrimidine derivative 4 , tetrazolo[1.5‐a][1,8]naphthyridine derivative 9 , pyrazolylpyrido[1,2‐a]pyrimidine derivatives 10a , 10b , 12 , pyrrolopyrido[1,2‐a]pyrimidine derivatives 14a , 14b , 14c , 14d , and 16a , 16b , starting from 2‐chloro‐4H‐4‐oxo‐pyrido[1,2‐a]pyrimidine ( 1 ), are described.     

Synthesis of Novel Pyrrolo[1′,5′‐a]‐1,8‐naphthyridine Derivatives through a Facile One‐Pot Process

Novel pyrrolo[1′,5′‐a]‐1,8‐naphthyridine compounds have been synthesized through a facile one‐pot process by the reaction of the corresponding 1,8‐naphthyridines with aliphatic anhydride. The structures were established by spectroscopic data. Further X‐ray crystal analysis of 4′‐acetyl‐7‐methyl‐pyrrolo[1′,5′‐a]‐1,8‐naphthyridine (1) identifies its intriguing molecular structure and reveals the strong π‐π stacking.     

Green Synthesis of Fused Imidazo[1,2‐a][1,8]naphthyridine Derivatives Catalyzed by DABCO under Solvent‐Free Solid‐State Conditions and Their Biological Evaluation

An efficient and eco‐friendly methodology has been developed for the construction of fused imidazo[1,2‐a][1,8]naphthyridine derivatives in the presence of 1,4‐diazabicyclo[2.2.2]octane, and involving various substituted heterocyclic amines with phenacyl bromide under solvent‐free solid‐state condition obtained the corresponding compounds ( 5a–g , 7a–f ) in short reaction time with high yield which is the important features of this protocol. All newly synthesized products were evaluated for their antibacterial and fungal activities. All these compounds displayed good antibacterial and antifungal activity. In predominantly, compounds 7e , 7d , and 5d demonstrate the highest antibacterial and antifungal activities. Furthermore, in silico molecular docking studies results were well complemented to the antimicrobial activity.     

Elaboration of 1,8‐naphthyridine‐2,7‐dicarboxaldehyde into novel 2,7‐dimethylimine derivatives

The known 1,8‐naphthyridine‐2,7‐dicarboxaldehyde was prepared by SeO₂ oxidation of 2,7‐dimethyl‐1,8‐naphthyridine. The dimethylated naphthyridine molecule was assembled from an adaptation of the Skraup synthesis using 2‐amino‐6‐methylpyridine and crotonaldehyde to afford a reproducible 37% yield, and constitute a significant advance over the literature of this reaction. The condensation of 1,8‐naph‐thyridine‐2,7‐dicarboxaldehyde with various primary amines (R = ‐C₆H₁₁, ‐CH₂C₆H₅, ‐C(CH₃)₃, ‐C₁₀H₁₅, and CH₂CH₂SCH₂CH₃) in alcohol affords diimines 1(a‐e) . The inherent crystallinity of 1(a‐e) affords pure compounds in reasonable to excellent yields (ca. 70%) after evaporation of solvent and recrystallization. The anticipated spectroscopic features of (N=C‐H) ¹H nmr shift and v(C=N) in the ir spectrum appear around 8.50 δ and 1640 cm^?1, respectively, for the series 1(a‐e) . These novel naph‐thyridines typically display the signature ¹H nmr doublets at ca. 8.15‐8.30 δ ascribed to the 3 and 4 naphthyridine protons, consistent with a mirror plane (through the quaternary carbons) perpendicular to the naphthyridine plane, and syn, syn relationships of the naphthyridine moiety with each imine nitrogen lone pair. Complexation studies of 1(a‐e) with transition metals of biological relevance such as copper(I) and copper(II) will be reported elsewhere.     

Facile and simple synthesis of some new polyfunctionally heterocyclic derivatives incorporating 2‐imino‐2H‐chromene moiety

1,2‐Dihydro‐2‐imino‐6‐(2‐imino‐2H‐chromen‐3‐yl)‐1,4‐diphenyl‐pyridine‐3‐carbonitrile 4 has been synthesized and reacted with ethyl cyanoacetate to yield the new 5‐amino‐1,7‐dihydro‐2‐(2‐imino‐2H‐chromen‐3‐yl)‐7‐oxo‐1,4‐diphenyl‐1,8‐naphthyridine‐6‐carbonitrile 6 , which consider a good and available starting intermediate for synthesis of series of functionalized chromenes. So, the compound 6 was utilized as a key for the synthesis of some new pyrimido[5,4‐c][1,8]naphthyridinones, pyrido[2,3‐c][1,6]naphthyridinones, triazolo[3′,4′:1,6]triazino][5,4‐c][1,8]naphthyridinones, triazolo[2′,3′:1,6]pyrimido[4,5‐c][1,8]naphthyridinones, triazepino[6,5‐c][1,8]naphthyridinone, and triazino[5,4‐c][1,8]naphthyridinones. The structures of these compounds were established by elemental analysis, IR, MS, and NMR spectral analysis. J. Heterocyclic Chem., (2012).     

Cyclometalated Iridium(III) and Rhodium(III) Complexes Containing Naphthyridine Ligands: Synthesis,Characterization and Biological Studies

The synthesis, crystal structure, and biological activity of new bis‐cyclometalated compounds [M(ptpy)₂(4‐chloro‐2‐methyl‐1,8‐naphthyridine)]PF₆ [M = Rh ( 1 ); M = Ir ( 2 ); ptpy = 2‐(p‐tolyl)pyridinato] and [M(ptpy)₂(2‐methyl‐1,8‐naphthyridine)]PF₆ [M = Rh ( 3 ); M = Ir ( 4 )] are described. The new compounds were prepared by the reaction of [{M(μ‐Cl)(ptpy)₂}₂] (M = Rh, Ir) with the corresponding naphthyridine ligands. The molecular structures of compounds 1 , 3 , and 4 were confirmed by single‐crystal X‐ray diffraction studies.     

Microwave‐assisted expeditious synthesis of novel benzo[b][1,8]‐naphthyridine‐3‐carbonitriles

A rapid and facile method for the synthesis of novel 5‐amino‐2‐sulfanyl tetrahydrobenzo[b][1,8]‐naphthyridine‐3‐carbonitrile derivatives has been developed by the treatment of 2‐amino‐3,5‐dicarbonitrile‐6‐sulfanyl pyridines with cyclohexanone in the presence of anhydrous aluminium chloride in dry dichloromethane under controlled microwave irradiation. J. Heterocyclic Chem., 00 , 00 (2011).     

Synthesis of 10‐amino‐9‐aryl‐2,3,4,5,6,7,9,10‐octahydroacridine‐1,8‐dione derivatives

A series of novel 10‐amino‐9‐aryl‐2,3,4,5,6,7,9,10‐octahydroacridine‐1,8‐dione derivatives 4 were synthesized by hydrazine or phenylhydrazine and 9‐aryl‐1,8‐dioxo‐2,3,4,5,6,7,9‐heptahydroxanthene derivatives 3 , which were prepared by 5‐substituted‐1,3‐cyclohexanedione 1 and aromatic aldehydes 2 in the presence of concentrated H₂SO₄ as a catalyst in water. The structures of all compounds were characterized by IR, MS, ¹H‐NMR, and elemental analysis, and the title compounds possess good fluorescence properties. J. Heterocyclic Chem., (2012).     

A novel binuclear copper complex incorporating a nalidixic acid derivative displaying a one‐dimensional coordination polymeric structure

The identification of the antibacterial action of nalidixic acid (nx) was central to the development of the quinolone antibacterial compounds. The ability of the nx naphthyridyl ring to interact with and inhibit some proteins has encouraged the investigation of similar structures in the search for more active compounds with less adverse effects. The possibility of structural modification by attachment of other biologically active moieties to the naphthyridyl ring of nx allowed the development of new active antimicrobial molecules. Hydrazone derivatives of nx can be synthesized easily based on the condensation of the hydrazide derivative of nx with the desired aldehyde or ketone. Only a few complexes with nx hydrazone derivatives have been described but for none were the crystal structures elucidated. The synthesis of a new one‐dimensional Cu^II coordination polymer, namely catena‐poly[[copper(II)‐di‐μ‐chlorido‐copper(II)‐{μ‐1‐ethyl‐N′‐[(1H‐imidazol‐4‐yl)methylidene]‐7‐methyl‐4‐oxo‐1,4‐dihydro‐1,8‐naphthyridine‐3‐carbohydrazidato}‐[dimethanolcopper(II)]‐{μ‐1‐ethyl‐N′‐[(1H‐imidazol‐3‐yl)methylidene]‐7‐methyl‐4‐oxo‐1,4‐dihydro‐1,8‐naphthyridine‐3‐carbohydrazidato}] dichloride methanol tetrasolvate], {[Cu₃(C₁₆H₁₅N₆O₂)₂Cl₂(CH₃OH)₂]Cl₂·4CH₃OH}_n, with the (1H‐imidazol‐4‐yl)methylidene carbohydrazide derivative of nalidixic acid (denoted h4imi), is presented and its structure is compared to the density functional theory (DFT) optimized structure of free h4imi. The title structure presents an octahedral Cu^II ion on an inversion centre alternating along a polymer chain with a square‐pyramidal Cu^II ion, with the two Cu^II centres bridged by two chloride ligands. Hydrogen bonds involving chloride counter‐ions and methanol solvent molecules mediate the three‐dimensional packing of the polymer. Comparison of the geometrical results from the structure analysis with those derived from a DFT study of the free ligand reveal the differences that arise upon coordination.     

Synthesis and In vitro Antitumor Screening of Novel 2,7‐Naphthyridine‐3‐carboxylic Acid Derivatives

New derivatives of 2,7‐naphthyridine‐3‐carboxylic acid were synthesized. We report the hydrolysis, chlorination, alkylation, and amination of the 2,7‐naphthyridine esters 1 , 2 . A series of Schiff's bases 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 9a , 9b , 9b' , 9c , 9d , 9e were produced by treating the obtained hydrazides 6 and 7 with aromatic aldehydes. The anticancer activities of the obtained derivatives were examined. Eighteen of the 24 newly synthesized compounds were qualified by the National Cancer Institute NCI (Bethesda, MD, USA) for in vitro screening against 60 different human tumor cell lines. The most active compound 8i was evaluated against a 60‐cell panel at five concentration levels and proved to be most sensitive towards central nervous system cancer (SF‐539), with GI₅₀ = 0.70 µmol, total growth inhibition = 5.41 µmol, and LC₅₀ = 53.7 µmol.     

Synthesis and characterization of new π‐conjugated polymers containing 1,8‐naphthyridine in the main chain: Role of the 1,8‐naphthyridine unit in π‐conjugated polymers

Alternating π‐conjugated copolymers of 1,8‐naphthyridine‐2,6‐diyl ( 1,8‐Nap ) with 9,9‐dioctylfluorene‐2,7‐diyl ( P(Flu‐Ph‐1,8‐Nap) ) and 2,5‐didodecyloxy‐1,4‐phenylene ( P(ROPh‐Ph‐1,8‐Nap) ) have been synthesized by Pd‐catalyzed organometallic polycondensation. The copolymers showed UV‐vis absorption peaks at around 390 nm in o‐dichlorobenzene. The polymers were photoluminescent both in o‐dichlorobenzene and in the solid state. In o‐dichlorobenzene, the emission peaks of P(Flu‐Ph‐1,8‐Nap) and P(ROPh‐Ph‐1.,8‐Nap) appeared at λ_EM = 440 and 471 nm, with quantum yields of 87% and 66%, respectively. Electrochemical data revealed that 1,8‐Nap behaved as a typical electron‐accepting unit. When P(Flu‐Ph‐1,8‐Nap) was treated with 10‐camphorsulfonic acid, the emission peak shifted to λ_EM = 598 nm. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

One‐Pot Synthesis of Fused [1,6]Naphthyridine Derivatives via Three‐Component Reaction

A simple, convenient, and eco‐friendly synthetic protocol has been developed via a one‐pot three‐component reaction between 2‐chloroquinoline‐4‐amines, different substituted aromatic aldehydes, and malononitrile using ethanol as reaction medium. Employing this protocol, a series of 5‐chloro‐4‐phenyl benzo[f ][1,6] naphthyridine‐2‐amino‐3‐carbonitrile derivatives were synthesized in an environmentally friendly approach under operational simplicity, short time reactions, easy work‐up procedure, and comparatively high yields. This chemistry provides a convenient and promising synthetic strategy for the construction of the napthyridine skeleton. All synthesized compounds were identified on the basis of their spectral data.     

A Divergent Synthesis of 1,8-Naphthyridines and Hydropyridopyrimidinones by the Reactions of o-Aminonitriles with Ketones

An efficient divergent synthesis of substituted 1,8‐naphthyridine and hydropyridopyrimidinone derivatives was developed by the reactions of o‐aminocyanopyridines and ketones based on different catalytic conditions.     

Synthesis,Structure, and Biological Activities of 10‐Substituted 3,3,6,6‐Tetramethyl‐9‐Aryl‐3,4, 6,7,9,10‐hexahydroacridine‐1,8(2H,5H)‐dione Derivatives

A series of 10‐substituted‐3,3,6,6‐tetramethyl‐9‐aryl‐3,4,6,7,9,10‐hexahydroacridine‐1,8(2H ,5 H )‐dione derivatives 2 were synthesized by reaction of compounds 1 with amines. The compounds 1 were effectively prepared by 5,5‐dimethylcyclohexane‐1,3‐dione and aldehydes in the presence of a little amount of L‐proline as catalyst at room temperature. All the compounds were characterized by IR, MS, and ¹H NMR. The crystal data of 1b and 2d were collected by X‐ray single‐crystal diffraction, and compounds 2b and 2d exhibited better inhibitory activity against HepG2 cells.