Synthesis,Antibacterial, and Antifungal Activities of Imidazo[2,1-c][1,2,4]triazoles and 1,2,4-Triazolo[4,3-a]pyrimidinones

A straightforward method has been developed for the synthesis of 1-phenyl-imidazo [2,1-c][1,2,4]triazole derivatives 5a–j and 1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidinones derivatives 6a–g starting from 5-amino-1-phenyl[1,2,4]triazole and p-toluenesulfonic acid (PTSA). This methodology affords a number of 1-phenyl-imidazo [2,1-c][1,2,4]triazoles 5a–j and 1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidinones 6a–g in reasonable yields and short reaction times. The structures of all new compounds were elucidated using infrared, ¹H and ¹³C NMR, and high-resolution mass spectrometry. Some of the newly synthesized compounds were screened for their antimicrobial activity.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications ^® for the following free supplemental resource(s): Full experimental and spectral details.]     

Synthesis of (1H)-3,4-Dihydropyrrolo[2,1-c][1,4]oxazin-1-one Derivatives

It has been found that some acyl derivatives of 1,2,3,4-tetrahydro-1-indolizin-1-one 1and (1H)-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one 2 show remarkable anti-inflammatory and analgesic activities1,2. The interest in extending the study of structure-activity relationships and search of new potent anti-inflammatory and analgesic agents led us to design and synthesize (1H)-3,4-dihydropyrrolo[2,1-c][1,4]oxazin-1-one 3 derivatives. NO 1 NNHO2 87654321ONO3 A few examples of the p…     

New Facile Route to Synthesize Furo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine and Furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine Derivatives

A new facile route for synthesis of 3-(aryl)-8,9-diphenylfuro[3,2-e][1,2,4]triazolo pyrimidines derivative from the same starting material, 2-amino-4,5-diphenylfuran-3-carbonitrile, has been developed through heterocyclization of the corresponding arylidene-hydrazono-5,6-diphenylfuro[2,3-d]pyrimidine and N-(arylmethylene)-4-imino-5,6-diphenylfuro[2,3-d]pyrimidin-3(4H)-amine under refluxing condition with acetic anhydride followed by air oxidation. The products were obtained in good yield with an easy workup along with the purification of products by a nonchromatographic method. This general synthetic procedure can be extended to the preparation of a wide range of isomeric triazoles using 2-amino 3-carbonitrile bifunctional derivatives.     

Synthesis and Anticonvulsant Activity of 9-Alkoxy-6,7-dihydro-2H-benzo[c][1,2,4]triazolo[4,3-a]azepin-3[5H]-ones

A series of novel 9-alkoxy-6,7-dihydro-2H-benzo[c][1,2,4]triazolo[4,3-a]azepin-3(5H)-one derivatives was designed and synthesized starting from 2,3,4,5-tetrahydro-7-hydroxy-1H-2-benzazepin-1-one. The structures of these compounds were confirmed by mass, ¹H NMR infrared spectra, and elemental analysis. Their anticonvulsant activity was evaluated by maximal electroshock (MES) test, and their neurotoxic effects were determined by the rotarod neurotoxicity test. The results shown that 3k was the most active compound with median effective dose (ED₅₀) of 27.3 mg/kg, median toxicity dose (TD₅₀) of 118.3 mg/kg, and protective index (PI) of 4.3. Possible structure–activity relationship is discussed.     

Synthesis of 4-arylcarbamoyl-5-(2-hydroxynaphthylazo)imidazoles and 1-substituted naphtho[2,1-e]imidazo[5,1-c][1,2,4]triazines

The reactions of β-naphthol with 5-diazoimidazoles and imidazolyl-5-diazonium salts containing chemically different carboxamide groups in position 4 were studied. Heterocyclization of 4-arylcarbamoyl-5-(2-hydroxynaphthylazo)imidazoles formed in these reactions was investigated. The presence of the NH fragment in the amide group prevents this process, the reaction giving instead 3-substituted 3,7-dihydroimidazo[4,5-d][1,2,3]triazin-4-ones, which is due to reversibility of C-azo coupling. Methods for modification of 1-ethoxycarbonyl group in the naphtho[2,1-e]imidazo[5,1-c][1,2,4]triazine system were developed and used to prepare substituted carboxamides inaccessible by other routes. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1208–1213, July, 2006.     

Crystal,molecular structure and tautomerism of (5-methyl-1H-[1,2,4]triazol-3-ylsulfanyl)-acetic acid

Molecular structure, relative stability of conformers, and tautomers of (5-methyl-1H-[1,2,4]triazol-3-ylsulfanyl)-acetic acid (MTSA) have been investigated by experimental (X-ray diffraction) and theoretical (B3LYP/aug-cc-pVDZ) methods. It was demonstrated that in the solid state MTSA exists in N1H tautomeric form. This tautomer is not the most stable in gas phase and its stabilization is provided by environment effects.     

Heteroannulated Quinazoline and Quinazolinone Derivatives from (Z)-2-[1-Benzamido-2-(3,4,5-trimethoxyphenyl)]vinyl-3,1-benzoxazin-4(3H)-one

The title compound 1 was prepared and allowed to react with a series of nitrogen nucleophiles to afford the quinazoline and quinazolinone derivatives 2–12 and tetrazole derivative 13. The IR, ¹H NMR, ¹³C NMR, and mass spectra of all the synthesized compounds were discussed.     

Synthesis of 5-Hydroxymethyl-8-methyl-3-(3-aryl-[1,2,4]oxadiazol-5-yl)-2H-pyrano[2,3-c]pyridin-2-ones and Their Esters

New 5-hydroxymethyl-8-methyl-3-(3-aryl-[1,2,4]oxadiazol-5-yl)-2H-pyrano-[2,3-c]pyridin-2-ones and their esters were synthesized. The structure of obtained compounds was determined through a complete ¹H NMR analysis.     

Synthesis and Crystal Structure of（Z）-2-Methyl-5,6-dihydrobenzo[d]thiazol-7（4H）-one O-Prop-2-yn-1-yl Oxime Derivatives

Compound(Z)-2-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one O-prop-2-yn-1-yl oxime, C11H12N2 OS, as a synthetic precursor of cytotoxic triazoles has been prepared and characterized by NMR spectra. Meanwhile, the crystal of IV was obtained and determined by X-ray single-crystal diffraction. Crystal data: monoclinic system, space group P21/c, a = 9.725(9), b = 8.068(7), c = 14.452(13)A, β = 98.68(2)°, V = 1120.9(17)A3, Z = 4, F(000) = 464, Dc = 1.305 g/cm3, μ = 0.263 mm-1, R = 0.0457 and w R = 0.1298 for 11511 independent reflections(Rint = 0.0709) and 2289 observed ones(I 2σ(I)).     

2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones

A novel method for synthesis of 2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 3-R-4,5-dihydro-1H-1,2,4-triazole-5-thiones with 3-aryl(heteryl)-2-propenoyl chlorides is proposed.     

Synthesis,Characterization and In Vitro Evaluation of Novel 5-Ene-thiazolo[3,2-b][1,2,4]triazole-6(5H)-ones as Possible Anticancer Agents

The present paper is devoted to the search for drug-like molecules with anticancer properties using the thiazolo[3,2-b][1,2,4]triazole-6-one scaffold. A series of 24 novel thiazolo-[3,2-b][1,2,4]triazole-6-ones with 5-aryl(heteryl)idene- and 5-aminomethylidene-moieties has been synthesized employing three-component and three-stage synthetic protocols. A mixture of Z/E-isomers was obtained in solution for the synthesized 5-aminomethylidene-thiazolo[3,2-b]-[1,2,4]triazole-6-ones. The compounds have been studied for their antitumor activity in the NCI 60 lines screen. Some compounds present excellent anticancer properties at 10 μM. Derivatives 2h and 2i were the most active against cancer cell lines without causing toxicity to normal somatic (HEK293) cells. A preliminary SAR study had been performed for the synthesized compounds.     

Facile and Convenient Synthesis of Pyrazole,Pyridine, Pyridazine,Pyrazolo[3,4-b]pyridine,and Pyrazolo[5,1-c][1,2,4]triazine Derivatives

Abstract

A convenient synthesis of a series of pyrazole, pyridine, pyridinethione, pyridazine, pyrazolo[3,4-b]pyridine, imidazo[1,2-a]pyrimidine, and pyrazolo[5,1-c][1 Kumar , R. 5-(1-Substituted)alkyl pyrimidine nucleosides as antiviral (herpes) agents . Curr. Med. Chem. 2004 , 11 , 2749 – 2766 . [Google Scholar] 2 Holy , A. ; Günter , J. ; Dvoráková , H. ; Masojídková , M. ; Andrei , G. ; Snoeck , R. ; Balzarini , J. ; De Clercq , E. Structure–antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues, 1: Derivatives substituted at the carbon atoms of the base . J. Med. Chem. 1999 , 42 , 2064 – 2086 . [Google Scholar] 4 Brandes , W. ; Daum , W. ; Krauss , P. Fungicidal oxime ethers. Ger. Patent 2,623,847, 1977; Chem. Abstr . 1978 , 88 , 120822h . [Google Scholar]]triazine derivatives incorporating a pyrimidine moiety, via the reactions of the versatile, readily accessible 3-oxo-N-(pyrimid-2-yl)butanamide with the appropriate reagents, is described.     

Synthesis and Biological Activities of 7‐Arylazo‐7H‐pyrazolo[5,1‐c][1,2,4] Triazol‐6(5H)‐Ones and 7‐Arylhydrazono‐7H‐[1,2,4]triazolo[3,4‐b] [1,3,4]thiadiazines

Two series of 7‐arylazo‐7H‐3‐(2‐methyl‐1H‐indol‐3‐yl)pyrazolo[5,1‐c][1,2,4]triazol‐6(5H)‐ones 4 and 7‐arylhydrazono‐7H‐3‐(2‐methyl‐1H‐indol‐3‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines 7 were prepared via reactions of 4‐amino‐3‐mercapto‐5‐(2‐methyl‐1H‐indol‐3‐yl)‐1,2,4‐triazole 1 with ethyl arylhydrazono‐chloroacetate 2 and N‐aryl‐2‐oxoalkanehydrazonoyl halides 5 , respectively. A possible mechanism is proposed to account for the formation of the products. The biological activity of some of these products was also evaluated.     

Anodic formation of 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 2(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles

3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles together with the unknown systems 2-(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles were obtained by anodic oxidation, under aprotic conditions, of aryl aldehyde N-(5-aryl-1,3,4-thiadiazol-2-yl) hydrazones. Mechanistic proposals are given.     

Improved microwave-assisted catalyst-free synthesis of 9-aryl-5,9-dihydropyrimido[4,5-d][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-dione derivatives

A green regioselective synthesis of some new and known 9-aryl-5,9-dihydropyrimido[4,5-d][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-diones has been described via the microwave-assisted one-pot reaction of 3-amino-1H-1,2,4-triazoles, aromatic aldehydes and barbituric acids under solvent- and catalyst-free conditions. This operationally simple procedure is less laborious and provides a better scope than previously reported procedures.     

Synthesis of 2-[2-(5-phenyl-1,2,4-oxadiazol-3-yl)-ethyl]benzimidazole and its x-ray analysis

Cyclization of O-benzoyl-2-(benzimidazol-1-yl)propioamidoxime under different temperature conditions gave 2-[2-(5-phenyl-1,2,4-oxadiazol-3-yl)ethyl]benzimidazole whose structure has been determined by X-ray analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1057–1061, July, 2006.     

Synthesis,Structure and Biological Activities of Novel 2‐(Trifluoromethyl)‐ 6‐arylimidazo[2,1‐b][1,3,4]‐thiadiazole (bis‐)Mannich Base Derivatives Containing Substitutedpiperazine Moiety

A convenient and practicable method for the synthesis of the novel 2‐(trifluoromethyl)‐6‐arylimidazo[2,1‐b][1,3,4]‐thiadiazole (bis‐)Mannich base derivatives containing various substitutedpiperazine motif has been developed based on the fused‐heterocycle intermediate. The new structures were identified through melting points, ¹H NMR, ¹³C NMR, ¹⁹F NMR, elemental analysis (or HRMS) and X‐ray single‐crystal diffraction. The pesticidal bioassays showed that some of compounds exhibited good fungicidal activities against Cercospora arachidicola, Physalospora piricola and Rhizoctonia cereali at 50 mg/L; some of them displayed favourable insecticidal activities against oriental armyworm (Mythimna separata Walker) at 200 mg/L, particularly, Vk and Vm with mortality rate of 75% and 80% respectively, could be considered as new insecticidal lead compounds for further structural optimization.     

One-Pot Synthesis and Fungicidal Activities of Derivatives of Imidazo [2,1-b]-1,3,4-thiadiazol-5(6H)-one

The isothiocyanates 2, obtained from aza-Wittig reactions of vinyliminophosphoranes 1 with CS ₂ , reacted with hydrazine to give 3-amino-2-thioxo-4-imidazolidinones 4. One-pot reactions of 4, aromatic isocyanates, Ph ₃ P, C ₂ Cl ₆ , and Et ₃ N generated imidazo[2,1-b]-1,3,4-thiadiazol-5(6H)-ones 7. Compound 7 exhibited good fungicidal activities, especially against Sclerotinia sclerotiorum de Bary and Botrytis Cinerea Pers.     

Synthesis and Crystal Structure of Ethyl 2-(6-(1,3-Dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) Butanoate

The title compound ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) butanoate 3 was synthesized by the reaction of ethyl 2-(6-amino-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) butanoate with 4,5,6,7-tetraydrophthalic anhydride,and its structure was determined by X-ray single-crystal diffraction.The crystal belongs to the monoclinic system,space group P21/n with a = 9.3469(2),b = 16.7715(5),c = 13.7153(4) ,β = 104.9680(10)°,μ = 0.107 mm-1,Mr = 430.42,V = 2077.08(10) 3,Z = 4,Dc = 1.376 g/cm3,F(000) = 904,T = 296(2) K,R = 0.0508 and wR = 0.1478.     

Synthesis of 8-aryl-1H-pyrazolo[4,3-e][1,2,4]triazolo[4,3-a] pyrimidine-4(5H)-imine by using the Preyssler''s anion [NaP5W30O110] as a green and eco-friendly catalyst

Reaction of 6-hydrazino-1,5-diphenyl-1H-pyrazolo[3,4-d]pyrimidine-4-imine with aromatic aldehyde in presence of Preyssler catalyst yielded 8-aryl-1H-pyrazolo[4,3-e][1,2,4]triazolo[4,3-a] pyrimidine-4(5H)-imine. The performance of different form of Preyssler's anions including H₁₄[NaP₅W₃₀O₁₁₀], H₁₄-P₅, mixed-addenda H₁₄[NaP₅W₂₉ MoO₁₁₀], H₁₄-P₅Mo, silica supported H₁₄[NaP₅W₃₀O₁₁₀]/SiO₂ and H₁₄-P₅/SiO₂ have been investigated. The reaction results were compared with that of a conventional acid catalyst (H₂SO₄).