Synthesis of imidazo[4,5-a]acridones and imidazo[4,5-a]acridines as potential antibacterial agents

Abstract  

New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug.     

R22(8) motifs in Aminopyrimidine sulfonate/carboxylate interactions: Crystal structures of pyrimethaminium benzenesulfonate monohydrate (2:2:1) and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate (4:2:2)

Background  

Pyrimethamine [2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine] is an antifolate drug used in anti-malarial chemotherapy. Pyrimidine and aminopyrimidine derivatives are biologically important compounds owing to their natural occurrence as components of nucleic acids.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones

Abstract  

The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species.     

Synthetic utility of a heterocyclic o-aminoaldehyde: synthesis of pyrazolopyridopyrimidines, pyrazolonaphthyridines, and pyrazolopyrimidonaphthyridinones

Abstract  

A series of various polysubstituted pyrazolo[3,4-h][1,6]naphthyridines, benzo[b]pyrazolo[3,4-h][1,6]naphthyridines, and pyrazolo[4′,3′:5,6]pyrido[4,3-d]pyrimidines were synthesized by Friedl?nder condensation of 4-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde (o-aminoaldehyde) with active methylene compounds. The o-aminoaldehyde was functionalized to o-aminonitrile and o-aminocarboxamide with malononitrile and cyanoacetamide, respectively, which on condensation with monosubstituted ureas and acetic anhydride, respectively, afforded pyrazolo[3,4-h]pyrimido[4,5-b][1,6]naphthyridines.     

Structural effects on the solid-state photodimerization of 5-chloro and 5-nitro-2(1<Emphasis Type="Italic">H</Emphasis>)-pyridone in molecular compounds

Abstract  

The preparation and crystal structure of six molecular compounds consist of light-stable host molecules [(1-cyclohexyl-4-hydroxybenzene, 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol, 4-((10-[4-(ethoxycarbonyl)phenoxy]decyl)oxy)benzene, 1,2,4,5-benzenetetracarboxylic acid, resorcinol] and light-sensitive guest molecules [(5-chloro-2(1H)-pyridone or 5-nitro-2(1H)-pyridone] are described in light of their failure to undergo [4 + 4] photodimerization in the solid-state upon irradiation with UV light. Unlike in many cases were pyridone and its derivatives undergo such dimerization in the solid-state due to the packing arrangement in the crystalline form in which the geometric requirement for photodimerization meet, the compounds described here failed to pack in ways to enable such photodimerization. The distances between the potentially reactive atoms ranged from 4.620 to 8.408 ? which are too long to react.     

Novel acenaphthopyrazine derivatives as antitumor agents against MCF-7 cells: molecular synthesis, optical properties, and DNA-binding studies

Abstract  

A series of novel acenaphthopyrazine derivatives was synthesized from acenaphthylene-1,2-dione via three steps, including bromination, cyclization, and S_NAr^H reaction. These new compounds exhibited potential antiproliferative activity against MCF-7 cells in vitro, and 3-[2-(dimethylamino)ethylamino]acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile exhibited the highest activity (IC ₅₀ = 4.60 μM). DNA-binding experiments suggested that these derivatives bind to DNA through intercalation with intrinsic binding constants K all above 10⁵ M⁻¹. Optical property studies indicated that these compounds have long emission wavelength (λ _em > 560 nm), high quantum yields in toluene (Φ_f = 0.59 for 3-(morpholin-4-yl)acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile), and large Stokes shift (ΔS > 130 nm).     

Synthesis and antibacterial studies of azodispersed dyes derived from 2-(thiazol-2-yl)phthalazine-1,4-diones

Abstract  

A dibenzobarrelene derivative was used as key intermediate for the synthesis of 2-(4-(methyl/phenylthiaz-ol-2-yl)-2,3,4a,5,10,10a-hexahydro-5,10-benzenobenzo[g]phthalazine-1,4-diones. These compounds were coupled with the appropriate diazonium chlorides to give the corresponding 5-(arylazo)thiazole derivatives. The synthesized dyes were applied to polyester as disperse dyes, and their antibacterial, color measurement, and fastness properties were evaluated.     

Synthesis and antimicrobial activity of tetrazolo[1,5-a]quinoline-4-carbonitrile derivatives

Abstract  

A series of new tetrazolo[1,5-a]quinoline-4-carbonitrile derivatives were synthesized for the first time via tetrazolo[1,5-a]quinoline derivatives. Elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectral data were used to elucidate the structures of all newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds were investigated against Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and two fungi, Candida albicans and Aspergillus niger, in comparison with standard drugs. Some of the tested compounds showed significant antimicrobial activity.     

Hydrazine-1-carbonitriles: new synthesis approach to and reactions with carbonyl compounds

Abstract  

A series of 1-(pyrimidin-2-yl)hydrazine-1-carbonitriles was synthesized by base-catalyzed condensation of 3,4-diamino-1,2,4-triazole hydrobromide with several 1,3-dinucleophilic compounds. These final products were formed by ring opening of the 1,2,4-triazolium ring via intermediate 3-amino[1,2,4]triazolo[1,5-a]pyrimidinium bromides.     

DBU-catalyzed expeditious and facile multicomponent synthesis of N-arylquinolines under microwave irradiation

Abstract  

N-Arylquinoline derivatives are obtained in excellent yields by a rapid, easy, and efficient one-pot multicomponent reaction of aromatic aldehydes, 3-arylamino-5,5-dimethylcyclohex-2-enone, and active methylene compounds utilizing 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a catalyst in ethanol under microwave irradiation.     

The synthesis of azole derivatives from 3-[(4-methylphenyl)amino]propanehydrazide and its N′-phenylcarbamoyl derivatives, and their antibacterial activity

Abstract  

5-[2-[(4-Methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-thione, 5-[2-[(4-methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-one, N-(2,5-dimethyl-1H-pyrrol-1-yl)-3-[(4-methylphenyl)amino]propanamide, and a series of N-[(phenylcarbamoyl)amino]-3-[(4-methylphenyl)amino]propanamides and 3-[(4-methylphenyl)(phenylcarbamoyl)amino]-N-[(phenylcarbamoyl)amino]propanamides, and their thio analogues were synthesized from 3-[(4-methylphenyl)amino]propanehydrazide. 1,3,4-Oxadiazole-2(3H)-thione was converted to 4-amino-2,4-dihydro-5-[2-[(4-methylphenyl)amino]ethyl]-3H-1,2,4-triazole-3-thione, whereas cyclization of N′-phenylcarbamoyl derivatives provided thiazole, oxadiazoles, and thiadiazole, as well as triazole derivatives. Two of the synthesized compounds exhibited good antibacterial activity against Rhizobium radiobacter.     

Microwave-assisted and scandium triflate catalyzed synthesis of tetrahydrobenzo[<Emphasis Type="Italic">a</Emphasis>]xanthen-11-ones

Abstract  

Synthesis of 12-aryl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-ones was achieved by one-pot condensation of β-naphthol, substituted benzaldehydes, and 1,3-dicarbonyl compounds catalyzed by Sc(OTf)₃ under microwave irradiation in excellent isolated yields. The catalyst was recycled up to four cycles with no appreciable loss in catalytic activity. The compounds were evaluated for Src kinase activity and anticancer activity.     

Synthesis and antiproliferative activity of multisubstituted N-fused heterocycles against the Hep-G2 cancer cell line

Abstract  

Pyrrolo[1,2-a]imidazole and pyrrolo[2,1-b]thiazole derivatives were synthesized in a one-pot procedure by [3 + 2] cycloaddition reactions of the corresponding imidazolium ylides and thiazolium ylides with an alkene followed by oxidative aromatization of the primary cycloadducts under the action of the mild oxidant tetrakispyridinecobalt(II) dichromate. Antiproliferative activity of 14 new bicyclic N-fused heterocycles against the human hepatocellular liver carcinoma (Hep-G2) cell line were examined by the MTT method. Some of the compounds showed favorable antiproliferative activity, especially compound 3i displayed potent antiproliferative activities with an IC₅₀ value of 0.36 μg/cm³.     

An experimental NMR and computational study of 4-quinolones and related compounds

Abstract  

We report the synthesis and structural study of eight compounds, either quinolin-4(1H)-ones or quinolines. Tautomerism as well as (E) → (Z) and rotational isomerism were studied both experimentally (¹H and ¹³C NMR) and theoretically [B3LYP/6-311++G(d,p)].     

A facile and efficient method for synthesis of xanthone derivatives catalyzed by HBF4/SiO2 under solvent-free conditions

Abstract  

HBF₄/SiO₂ was used as an efficient, green, and inexpensive catalytic system for synthesis of 12-aryl or 12-alkyl-8,9,10,12-tetrahydro-11H-benzo[a]xanthen-11-one derivatives via a one-pot three-component reaction of aldehydes, 2-naphthol, and cyclic 1,3-dicarbonyl compounds. The reactions proceeded rapidly at 80 °C under solvent-free conditions and the desired products were obtained in good to excellent yields.     

Aldimines of 5-aminouracil as reagents in 1,3-dipolar cycloaddition reaction

Abstract  

The condensation of 5-aminouracil with aromatic aldehydes gave the appropriate C-arylimines, which were used in [2+3] cycloaddition with nitrile oxides derived from 4-substituted benzaldoximes. As a result of the dipolar cycloaddition reaction several hitherto unknown 5-(3,5-diphenyl-1,2,4-oxadiazol-4(5H)-yl)pyrimidine-2,4(1H,3H)-diones have been obtained in satisfactory yields.     

Synthesis, complete NMR spectral assignments, and antifungal screening of new 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one oxime derivatives

Abstract  

A series of differently substituted 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one oximes have been synthesized and their ¹H and ¹³C NMR chemical shifts have been unambiguously assigned using H,H-COSY, NOESY, HSQC, and HMBC spectral data. On the basis of the NMR studies, irrespective of the nature and position of the substituents, all reported compounds exist in twin-chair conformation with equatorial disposition of the phenyl groups at C-2 and C-4 of the 3-azabicyclononane moiety. Among the synthesized oxime derivatives, compounds with halo-substituents at ortho/para positions of the phenyl showed good antifungal profile against all tested organisms.     

Synthesis of 8-oxoprotoberberines using acid-mediated cyclization or the Heck reaction

Abstract  

A facile method of synthesizing 8-oxoprotoberberines is described from 6-benzoyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline-5-carbaldehyde via acid-mediated cyclization or from 2-(2-iodophenethyl)isoquinolin-1(2H)-one via the Heck reaction. The present method offers several advantages, such as good yields and a simple procedure.     

Synthesis and anticancer activity of some 1,5-diaryl-3-(3,4,5-trihydroxyphenyl)-1H-pyrazolo[4,3-e][1,2,4]triazines

Abstract  

The deregulation of cell cycle components in cancer cells has provided a rationale for the development of small molecule inhibitors of cyclin-dependent kinases as novel anticancer drugs. A series of 1,5-diaryl-3-(3,4,5-trihydroxyphenyl)-1H-pyrazolo[4,3-e][1,2,4]triazines was synthesized and their kinase inhibitory activity and cytotoxicity against several cancer cell lines has been evaluated. Some of the compounds of the series exhibited induction of caspase-dependent cell death and inhibition of cyclin-dependent kinase 2 (CDK2).     

Synthesis of 5-spirocyclohexyl-2,4-dithiohydantoin derivatives: a potential anti-leishmaniasis agent

Abstract  

A series of spiro-dithiohydantoins were synthesized by heating a mixture of 5-spirocyclohexyl-2,4-dithiohydantoin potassium salt and 3-chloropropanoyl chloride. These compounds were synthesized and evaluated for their activity against five Leishmanial strains in the promastigote stage in vitro. Seventy-two hours inoculation of a variety of products gave an IC ₁₀₀ and average IC ₅₀ values of 1.25 and 0.376 mg/cm³ against all Leishmanial strains tested.