Recognition of guanine-guanine mismatches by the dimeric form of 2-amino-1,8-naphthyridine.

Dimeric 2-amino-1,8-naphthyridine selectively binds to a G-G mismatch with high affinity (K(d) = 53 nM). We have investigated a binding mechanism of naphthyridine dimer 2 to a G-G mismatch by spectroscopic studies, thermodynamic analysis, and structure-activity studies for the thermal stabilization of the mismatch. 1H NMR spectra of a complex of 2 with 9-mer duplex d(CATCGGATG)2 containing a G-G mismatch showed that all hydrogens in two naphthyridine rings of 2 were observed upfield compared to those of 2 in a free state. The 2D-NOESY experiments showed that each naphthyridine of 2 binds to a guanine in the G-G mismatch within the pi-stack. In CD spectra, a large conformational change of the G-G mismatch-containing duplex was observed upon complex formation with 2. Isothermal calorimetry titration of 2 binding to the G-G mismatch showed that the stoichiometry for the binding is about 1:1 and that the binding is enthalpy-controlled. It is clarified by structure-activity studies that show (i) the linker connecting two naphthyridine rings was essential for the stabilization of the G-G mismatch, (ii) the binding efficiency was very sensitive to the linker structure, and (iii) the binding of two naphthyridines to each one of two Gs in the G-G mismatch is essential for a strong stabilization. These results strongly supported the intercalation of both naphthyridine rings of 2 into DNA base pairs and the formation of a hydrogen bonded complex with the G-G mismatch.     

Synthesis and evaluation of fluorogenic 2-amino-1,8-naphthyridine derivatives for the detection of bacteria

Several novel fluorogenic N-aminoacylnaphthyridine substrates were synthesized in good yield and tested for their ability to detect pathogenic bacteria in agar-based cell culture. Simple 2-N-(β-alanyl)amino-5,7-dialkylnaphthyridine substrates were selectively hydrolysed by β-alanylaminopeptidase expressing bacteria, but were subject to diffusion in the agar medium. Diffusion was reduced in the 2-N-(β-alanyl)amino-7-alkylnaphthyridine substrates with longer alkyl chains, but inhibition of growth was increased. 2-N-(β-Alanyl)amino-7-octylnaphthyridine inhibited the growth of all species tested, except for strains resistant to colistin/polymyxin, providing a rationale for the development of substrates for the selective detection of drug resistant species in clinical samples.     

Unusual multi-component condensation in the synthesis of 1,4-dihydro-1,6-naphthyridine derivatives

Multi-component condensation of cyanoselenoacetamide with ethyl 2-furfuryl-idenacetoacetate and liquid alkyl halides, catalyzed byN-methylmorpholine, affords 7-alkylseleno-5-amino-8-cyano-3-ethoxycarbonyl-4-(2-furyl)-2-methyl-1,4-dihydro-1,6-naphthyridines, which have not been described hitherto. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 121–124, January, 2000.     

Unusual multi-component condensation in the synthesis of 1,4-dihydro-1,6-naphthyridine derivatives

Multi-component condensation of cyanoselenoacetamide with ethyl 2-furfuryl-idenacetoacetate and liquid alkyl halides, catalyzed byN-methylmorpholine, affords 7-alkylseleno-5-amino-8-cyano-3-ethoxycarbonyl-4-(2-furyl)-2-methyl-1,4-dihydro-1,6-naphthyridines, which have not been described hitherto. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 121–124, January, 2000.     

Synthesis of 7-aryl-1,8-naphthyridines via addition of aryl boronic acids to 1,8-naphthyridine N-oxides

Simply combining aryl boronic acids with 1,8-naphthyridine N-oxides and heating at 110 °C in toluene or dimethylformamide affords the corresponding 7-aryl-1,8-naphthyridines. The reaction is not sensitive to air or moisture and the process can be extended to other electron-deficient heteroaromatic N-oxides.     

Eco-friendly synthesis of 1,8-naphthyridine 5-aryl-1,3,4-oxadiazole derivatives under solvent-free solid-state conditions and their antimicrobial activity

Research on Chemical Intermediates - A simple and highly efficient green synthetic procedure has been described for the construction of...     

An intramolecular cyclization of 7-substituted 6-fluoro- 1,8-naphthyridine and -quinoline derivatives

A synthesis of 1,4-oxazine and pyrazine ring systems by an intramolecular cyclization of 7-substituted 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine and -quinoline derivatives having a nitrogen or oxygen nucleophilic site in the C-7 appendage was studied. The in vitro antibacterial activities of compounds prepared by this method were tested.     

Pyrrolization processes of vinyl substituted imidazo[1,2-a]pyridine,pyrimidine and 1,8-naphthyridine

A general synthesis for the preparation of a series of N-bridgehead compounds: pyrroloimidazopyridine, pyrimidine and naphthyridine has been developed beginning with azidovinyl compounds with thermolytic or photochemical methods     

Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for alphaVbeta3 integrin antagonists

The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.     

Ratiometric fluorescence detection of pyrimidine/purine transversion by using a 2-amino-1,8-naphthyridine derivative.

A new class of abasic site-binding fluorescence ligands, Naph-NBD in which 7-nitrobenzo-2-oxa-1,3-diazole (NBD) is connected to 2-amino-7-methyl-1,8-naphthyridine (Naph) by a propylene linker, is presented for the ratiometric assay for SNPs typing. In solutions buffered to pH 7.0 (I = 0.11 M, at 5 degrees C), Naph-NBD is found to selectively recognize pyrimidine bases over purine bases opposite the abasic site in DNA duplexes (K11/M(-1): T, 8.1 x 10(6); C, 2.5 x 10(6): G, 0.33 x 10(6); A, 0.27 x 10(6)). The binding of Naph-NBD is accompanied by significant quenching of the fluorescence from the naphthyridine moiety (lambda max, 409 nm), while the emission from the NBD (lamda max, 544 nm) is relatively unaffected. Such a fluorescence response of Naph-NBD allows the emission ratio detection of pyrimidine/purine transversion.     

Selective acetylation of substituted (E)-4(1H)-hydroxyimino-2,3-dihydro-1,8-naphthyridine

We report a selective acetylation of compounds 2 in 1-, 4- or 1,4-position. The treatment of 2 with acetic anhydride gave the compounds 3 and with acetyl chloride the compounds 4 . The 1-acetyl derivatives were obtained starting from 5 via the oxime derivatives 6, 7 and 8 . Tests on phytoiatric antimycotic activity and on reactivation of phosphylated acetylcholinesterase and inhibition of acetylcholinesterase were performed.     

A three-component,one-pot synthesis of 1,8-naphthyridine and isoxazole derivatives and computational elucidation of the mechanism

Research on Chemical Intermediates - An efficient and general method for the synthesis of substituted 3,4-dimethylisoxazolo[5,4-b]pyridine-5-carboxamide and benzo[b][1,8]naphthyridine-3-carboxamide...     

Efficient one-pot synthesis of substituted 2-amino-1,3,4-oxadiazoles

A convenient one-pot method for the preparation of substituted 2-amino-1,3,4-oxadiazoles has been developed. The method is a significant improvement over previously reported syntheses. Reaction of carboxylic acids with thiosemicarbazides afforded the corresponding oxadiazoles in moderate to good yields. In general, the products precipitated from the reaction mixture, and were collected by filtration. In most of the cases, no chromatographic separations were required. To explore the scope and limitations of this reaction, various aliphatic, aromatic, and heteroaromatic carboxylic acids were reacted with different substituted thiosemicarbazides. The influence of R¹ and R² substituents on the reaction yield and additional results demonstrating the versatility of this method are presented.     

Unusual reaction of 1,8-diazabicyelo-[5.4.0]undec-7-ene with diethyl maleate

Michael addition of DBU on diethyl maleate and subsequent cyclization of the adduct afforded a tricyclic derivative which was susceptible to react further with a second molecule of unsaturated diester.     

4-amino-2-phenylindole-based compounds with potential antibacterial activity

Primary condensation of 4-amino-2-phenylindole with ethyl acetoacetate and 4,4,4-trifluoroacetoacetate resulted in corresponding amides, which under acidic conditions were converted to pyrrolo[2,3-h]quinolones. Antibacterial activity of the amide obtained from aminoindole and ethyl 4,4,4-trifluoroacetylacetate was detected.     

Pd（OAc）2 catalyzed synthesis of heteroaryl-substituted 1,8-naphthyridine derivatives via C-N-coupling reactions of chloronaphthyridines

An efficient route to synthesize the heteroaryl-substituted 1,8-naphthyridine derivatives was described.Eight 2-heteroaryl-and 2,7-diheteroaryl-1,8-naphthyridine derivatives were obtained through palladium-catalyzed C-N-coupling reactions of chloro-naphthyridines with imidazole,benzimidazole,morpholine,3,5-dimethylpyrazole,and phthalimide in moderate to good yields.     

One-pot synthesis of substituted 3-amino-2-nitrothiophenes and selenophenes

In this work, we described an easy preparation of substituted 3-amino-2-nitrothiophenes and selenophenes. Substituted β-chloroacrylonitriles were reacted with sodium sulfide or sodium selenide and bromonitromethane to yield the expected compounds in a one-pot three-step procedure in good yields.