Synthesis and antifungal activity of novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b][1,2,4]triazepines

5‐Aryl‐3,4‐diamino‐1,2,4‐triazoles 5 on treatment with β‐chlorocinnamaldehydes 7 in the presence of catalytic amount of p‐TsOH and N,N‐dimethylformamide as an energy transfer medium under microwave irradiation and as solvent with oil‐bath heating at 80 °C affords novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b]‐1,2,4]triazepines 8 . The structures of the synthesized compounds were established on the basis of ¹H NMR, IR, mass spectral data and elemental analysis.     

Conformational polymorphs of 3‐cyclopropyl‐5‐(3‐methyl‐[1,2,4]triazolo[4,3‐a]pyridin‐7‐yl)‐1,2,4‐oxadiazole

The dipharmacophore compound 3‐cyclopropyl‐5‐(3‐methyl‐[1,2,4]triazolo[4,3‐a]pyridin‐7‐yl)‐1,2,4‐oxadiazole, C₁₂H₁₁N₅O, was studied on the assumption of its potential biological activity. Two polymorphic forms differ in both their molecular and crystal structures. The monoclinic polymorphic form was crystallized from more volatile solvents and contains a conformer with a higher relative energy. The basic molecule forms an abundance of interactions with relatively close energies. The orthorhombic polymorph was crystallized very slowly from isoamyl alcohol and contains a conformer with a much lower energy. The basic molecule forms two strong interactions and a large number of weak interactions. Stacking interactions of the `head‐to‐head' type in the monoclinic structure and of the `head‐to‐tail' type in the orthorhombic structure proved to be the strongest and form stacked columns in the two polymorphs. The main structural motif of the monoclinic structure is a double column where two stacked columns interact through weak C—H…N hydrogen bonds and dispersive interactions. In the orthorhombic structure, a single stacked column is the main structural motif. Periodic calculations confirmed that the orthorhombic structure obtained by slow evaporation has a lower lattice energy (0.97 kcal mol^?1) compared to the monoclinic structure.     

Synthesis and antitumor activities of 2‐(substituted)phenyl‐1,2,4‐triazolo[1,5‐a]pyridines

Twenty‐three 2‐(substituted)phenyl‐1,2,4‐triazolo[1,5‐a]pyridines have been synthesized by cycloadditison reaction between N‐amino methylpyridinium mesitylenesulfonates and substituted benzonitriles under the presence of potassium hydroxide at room temperature. The structures of all products were confirmed by ¹H NMR, MS and elemental analyses. The antitumor activities of these compounds were evaluated against human ovary cancer cell line (HO‐8910) in vitro by MTT method. The preliminary results showed that compound 1e (IC₅₀ 28μM) and compound 1w (IC₅₀ 31μM) exhibited stronger antitumor activities than cisplatin (IC₅₀ 35μM) in vitro. Hence, 1e and 1w have potential antitumor activities and are worth further investigation.     

3‐[5‐(4‐Chlorophenyl)‐1‐(4‐methoxyphenyl)‐1H‐pyrazol‐3‐yl]propionic acid and the corresponding methyl ester

The synthesis of 3‐[5‐(4‐chlorophenyl)‐1‐(4‐methoxyphenyl)‐1H‐pyrazol‐3‐yl]propionic acid, C₁₉H₁₇ClN₂O₃, (I), and its corresponding methyl ester, methyl 3‐[5‐(4‐chlorophenyl)‐1‐(4‐methoxyphenyl)‐1H‐pyrazol‐3‐yl]propionate, C₂₀H₁₉ClN₂O₃, (II), is regiospecific. However, correct identification of the regioisomer formed by spectroscopic techniques is not trivial and single‐crystal X‐ray analysis provided the only means of unambiguous structure determination. Compound (I) crystallizes with Z′ = 2. The propionic acid groups of the two crystallographically unique molecules form a hydrogen‐bonded dimer, as is typical of carboxylic acid groups in the solid state. Conformational differences between the methoxybenzene and pyrazole rings give rise to two unique molecules. The structure of (II) features just one molecule in the asymmetric unit and the crystal packing makes greater use than (I) of weak C—H...A interactions, despite the lack of any functional groups for classical hydrogen bonding.     

Synthesis and pharmacological investigation of novel 4‐(4‐Ethyl phenyl)‐1‐substituted‐4H‐[1,2,4]triazolo[4,3‐a]‐quinazolin‐5‐ones as new class of H1‐antihistaminic agents

A series of novel 4‐(4‐ethylphenyl)‐1‐substituted‐4H‐[1,2,4]triazolo[4,3‐a]quinazolin‐5‐ones were synthesized by the cyclization of 2‐hydrazino intermediate with various electrophile. The starting material 2‐hydrazino compound was synthesized from 2‐ethyl aniline by a new innovative route with improved yield. When tested for their in vivo H₁‐antihistaminic activity on conscious guinea pigs, all the test compounds significantly protected the animals from histamine induced bronchospasm. The compound II emerged as the most active compound of the series and it is more potent (73.93% protection) when compared to the reference standard, chlorpheniramine maleate (71% protection), it showed negligible sedation (10%) when compared to chlorpheniramine maleate (30%). Therefore compound II will serve as prototype molecule for further development as a new class of H₁‐antihistamines     

Synthesis and Characterization of Novel 1‐Methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazole Derivatives

A series of novel 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles was synthesized in three steps from 5‐(1‐methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones. 5‐(1‐Methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones were converted into 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles upon methylation followed by treatment with aq. KMnO₄. The reaction of 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles with Raney nickel resulted in desulphonylation to afford corresponding 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles. All the new synthesized compounds were characterized by spectral techniques.     

Synthesis of Novel Fluorescent 2‐{4‐[1‐(Pyridine‐2‐yl)‐1H‐pyrazol‐3‐yl] phenyl}‐2H‐naphtho [1,2‐d] [1,2,3] triazolyl Derivatives and Evaluation of Their Thermal and Photophysical Properties

Novel 2‐{4‐[1‐(pyridine‐2‐yl)‐1H‐pyrazol‐3‐yl] phenyl}‐2H‐naphtho [1,2‐d] [1,2,3] triazolyl fluorescent derivatives were synthesized from p‐nitrophenylacetic acid and 2‐hydrazino pyridine through Vilsmeier–Haack and diazotization reactions. Photophysical properties were evaluated, and results show that compounds have good fluorescence quantum yields. Thermal analysis showed that they are reasonably stable. The structures of the compounds were confirmed by FT‐IR, ¹H NMR, ¹³C NMR, and mass spectral and elemental analysis.     

Synthesis of 4(pyrazol-3-yl)[1,2,4]triazolo[4,3-a]quinoxalines and tetrazolo analog

The transformation of 2-chloro-3-[5-(acetoxymethyl)-1-phenylpyrazol-3-yl]quinoxaline 3 to 1-aryl-4-[5-(hydroxymethyl-1-phenylpyrazol-3-yl][1,2,4]triazolo[4,3-a]quinoxalines 4a-c has been achieved upon treatment with aroylhydrazines in boiling butanol. Compounds 4a-c were smoothly acetylated by acetic anhydride to give their acetyl derivatives 5a-c in good yield. 4-[5-(Acetoxymethyl)-1-phenylpyrazol-3-yl]-1-methyl[1,2,4]triazolo[4,3-a]quinoxaline was prepared by ring closure of 2-hydrazino-3-[5-(hydroxymethyl)-1-phenylpyrazol-3-yl]quinoxaline 6 by the action of acetic anhydride. The reaction of 6 with acetylacetone afforded 3-[5-(hydroxymethyl)-1-phenylpyrazol-3-yl]-2-(3,5-dimethylpyrazol-1-yl)quinoxaline 8 . In addition, the reaction of 3 with sodium azide in boiling N, N-dimethylformamide yielded the fused tetrazolo[1,5-a]quinoxaline 9 .     

Design,synthesis and biological evaluation of novel 6,7,8,9‐tetrahydro‐2‐(2‐aryloxypyrimidin‐4‐yl)‐2H‐[1,2,4]triazolo[4,3‐a]azepin‐3(5H)‐ones

A series of novel 6,7,8,9‐tetrahydro‐2‐(2‐aryloxypyrimidin‐4‐yl)‐2H‐[1,2,4]triazolo[4,3‐a]azepin‐3(5H)‐ones were designed and efficiently synthesized. Their structures were determined by IR, ¹³C and ¹H NMR, mass spectroscopy, and elemental analysis. These compounds were screened for herbicidal activities against rape and barnyard grass. Compounds 5a‐5f and 5m exhibited moderate herbicidal activity against rape. In addition, the synthesis of the intermediate 1‐(azepan‐2‐ylidene)‐2‐(2‐chloropyrimidin‐4‐yl)‐hydrazine ( 3 ) was studied and the reason for the low yield in the initial procedure is discussed as well.     

Synthesis of Novel 3‐(3‐(5‐Methylisoxazol‐3‐yl)‐7H‐[1,2,4]Triazolo [3,4‐b][1,3,4]Thiadiazin‐6‐yl)‐2H‐Chromen‐2‐Ones

A novel series of coumarin substituted triazolo‐thiadiazine derivatives were designed and synthesized by using 5‐methyl isoxazole‐3‐carboxylic acid ( 1 ), thiocarbohydrazide ( 2 ), and various substituted 3‐(2‐bromo acetyl) coumarins ( 4a , 4b , 4c , 4e , 4d , 4f , 4g , 4h , 4i , 4j ). Fusion of 5‐methyl isoxazole‐3‐carboxylic acid with thiocarbohydrazide resulted in the formation of the intermediate 4‐amino‐5‐(5‐methylisoxazol‐3‐yl)‐4H‐1,2,4‐triazole‐3‐thiol ( 3 ). This intermediate on further reaction with substituted 3‐(2‐bromo acetyl) coumarins under simple reaction conditions formed the title products 3‐(3‐(5‐methylisoxazol‐3‐yl)‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl‐2H‐chromen‐2‐ones ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j ) in good to excellent yields. All the synthesized compounds were well characterized by physical, analytical, and spectroscopic techniques.     

4‐[1‐(Phenylsulfonyl)indol‐3‐yl]‐3a,4,5,9b‐tetrahydro‐3H‐cyclopenta[c]quinoline

In the title compound, C₂₆H₂₂N₂O₂S, the tetra­hydro­pyridine ring has a conformation intermediate between half‐chair and sofa. The tetrahydroquinoline mean plane makes a dihedral angle of 73.3 (1)° with the cyclopentene ring, which adopts an envelope conformation, and an angle of 45.45 (4)° with the indole best plane. The dihedral angle between the benzene and pyrrole rings is 2.6 (1)°. The orientations of the phenyl ring on the sulfonyl group and of the indole are governed by weak C—H?O interactions. The packing of the mol­ecule in the solid state is stabilized by C—H?O and C—H?N hydrogen bonds.     

Synthesis of new 1‐phenylthieno[1,2,4]triazolo[4,3‐a]pyrimidin‐5(4H)‐one derivatives

A series of novel 1‐phenylthieno[1,2,4]triazolo[4,3‐a]pyrimidin‐5(4H)‐one derivatives 5 and 6 were synthesized by oxidative cyclization of thienopyrimidinonyl hydrazones using iodobenzene diacetate. J. Heterocyclic Chem., (2011).     

Synthesis of mesoionic triazolo[4,3-a]quinoxalines

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 1 or 6-chloro-2-(1-methylhydrazino)-quinoxaline 5 with phenyl isothiocyanate under reflux in N,N-dimethylformamide gave 7-chloro-3-methyl-1,2,4-triazolo[4,3-a]quinoxalin-3-ium-1-thioate 4 , which was also obtained by refluxing of 6-chloro-2-[1-methyl-2-(N-phenylthiocarbamoyl)hydrazino]quinoxaline 4-oxide 2b or 6-chloro-2-[1-methyl-2-(N-phenylthiocarbamoyl)hydrazino]quinoxaline 6 in N,N-dimethylformamide.     

Synthesis and antitumor activity of new 1,2,4‐triazine and [1,2,4]triazolo[4,3‐b][1,2,4]triazine derivatives and their thioglycoside and acyclic C‐nucleoside analogs

New 1,2,4‐triazine and their derived 1,2,4‐triazolo[3,4‐b][1,2,4]triazine derivatives were synthesized starting from 5,6‐diphenyl‐1,2,4‐triazine‐3‐thiol. Furthermore, the corresponding 1,2,4‐triazolo[3,4‐b][1,2,4]‐triazine thioglycosides and acyclic C‐nucleoside analogs were synthesized. The newly synthesized compounds were evaluated for their antitumor activity and some of them showed high inhibition activities. J. Heterocyclic Chem., 2011.     

Synthesis and Antimicrobial Screening of Some Novel 2‐(5‐(4‐(1H‐Benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenols Incorporated by Triazole Moiety

A novel series of 2‐(5‐(4‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)phenols derivative has been synthesized from (E)‐3‐(4‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)phenyl)‐1‐(2‐hydroxyphenyl)prop‐2‐en‐1‐ones in ethanol and hydrazine hydrate under reflux condition. The synthesized compounds were screened for antibacterial activity against Gram‐positive bacteria viz Staphylococcus aureus and Bacillus subtilis and Gram‐negative bacteria viz Escherichia coli and Salmonella typhi, respectively. Some of the tested compounds showed significant antimicrobial activity. IR, ¹H NMR, mass spectral data, and elemental analysis elucidated the structures of all the newly synthesized compounds.     

Synthesis and herbicidal activity of 2‐(3‐(trifluoromethyl)‐5‐(alkoxy)‐1H‐pyrazol‐1‐yl)‐4‐aryloxypyrimidine derivatives

A series of 2‐(3‐(trifluoromethyl)‐5‐(alkoxy)‐1H‐pyrazol‐1‐yl)‐4‐aryloxypyrimidine derivatives were designed and synthesized. The structures of all the title compounds were confirmed by ¹H NMR and elementary analysis. These compounds were screened for herbicidal activity against rape and barnyard grass. Compound B13 exhibited moderate herbicidal activity.     

Synthesis of 1,3,3a,5‐tetraaryl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a] [1,5]benzodiazepines

A series of 3a,5‐diaryl‐1,3‐diphenyl‐3a,4,5,6‐tetrahydro‐3H‐1,2,4‐triazolo[4,3‐a][1,5]benzo‐diazepines was synthesized by the cycloaddition reactions of 2,4‐diaryl‐2,3‐dihydro‐1H‐1,5‐benzo‐diazepines and N‐phenylbenzonitrileimine generated from N‐phenylbenzenecarbohydrazonic chloride in the presence of triethylamine in anhydrous tetrahydrofuran. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:557–559, 2001     

Regioselective synthesis and characterization of new 3‐aryl‐7‐trifluoromethyl‐[1,2,4]triazolo[4,3–a]pyrimidines

The regioselective synthesis and characterization of a new series of 3‐aryl‐7‐trifluoromethyl[1,2,4]triazolo[4,3–a]pyrimidines from the oxidative heterocyclization of 2‐(N′‐benzylidenehydrazino)‐4‐trifluoromethylpyrimidines with copper dichloride is described. J. Heterocyclic Chem., (2011).     

Synthesis and Spectral Characteristics of Novel Fluorescent Dyes Based on Pyrimido[4,5‐d] [1,2,4]triazolo[4,3‐a]pyrimidine

Different derivatives of a novel heterocyclic system, i.e., pyrimido[4,5‐d] [1,2,4]triazolo[4,3‐a]pyrimidine, are synthesized in moderate‐to‐good yields. These compounds exhibit excellent photochromism upon photoirradiation. The photophysical characterizations of these new compounds were evaluated by UV/VIS absorption and fluorescence emission studies. The emission spectra in various solvents are also presented and discussed. The changes are due to the intramolecular H‐bonding of pyrimido‐triazolo‐pyrimidine with H₂O, and photoinduced electron and general solvent effect. These compounds display high fluorescence quantum yields and are reported as new fluorophores.