Tetrazole Derivatives Research Articles

First report of the direct supporting of palladium–arginine complex on boehmite nanoparticles and application in the synthesis of 5‐substituted tetrazoles

Boehmite nanoparticles are aluminium oxide hydroxide (γ‐AlOOH) particles, which were prepared using a simple and inexpensive procedure in water at room temperature and further modified using arginine. Subsequently palladium particles were immobilized on their surface to prepare Pd‐Arg@boehmite. This novel nanostructured compound was fully characterized using thermogravimetric analysis, X‐ray diffraction, inductively coupled plasma optical emission (ICP‐OES) and energy‐dispersive X‐ray spectroscopies, and scanning and transmission electron microscopies. Finally, this catalyst was applied as a moisture‐ and air‐stable heterogeneous material for the synthesis of 5‐substituted 1H–tetrazole derivatives. The leaching of palladium and heterogeneity of the catalyst were studied using hot filtration and ICP‐OES. This catalyst demonstrated remarkable recyclability. The novelty of this work is that it represents the first time an amino acid has been grafted on boehmite nanoparticles.

ChemInform Abstract: Tuning the Topology of Hybrid Inorganic—Organic Materials Based on the Study of Flexible Ligands and Negative Charge of Polyoxometalates: A Crystal Engineering Perspective

AbstractReview: 159 refs.

Synthesis of novel tetrazole derivatives and evaluation of their antifungal activity

With the appearance of the antifungal resistance, novel antifungal agents need to be identified. In this context new 2,5-disubstituted tetrazole derivatives containing benzothiazole, benzoxazole or phenylsulfonyl moiety were synthesized by N-alkylation of aryltetrazole with 2-[(3-chloropropyl)sulfanyl]-1,3-benzothiazole or 2-[(3-chloropropyl)sulfanyl]-1,3-benzoxazole and Michael-type addition of aryltetrazole to phenyl vinyl sulfone. The chemical structures of the synthesized compounds were confirmed by means of 1H NMR, 13C NMR, IR and HRMS spectral data. The compounds were tested against the moulds: Fusarium sambucinum, Fusarium oxysporum, Colletotrichum coccodes, Aspergillus niger, and the yeast Candida albicans. The results showed that among the moulds only C. coccodes was significantly sensitive to all the structures examined. All the tetrazole derivatives acted at the same level against C. albicans and demonstrated a high cell growth inhibition (97–99%) at the concentrations ranging from 16 to 0.0313μg/mL. The mode of action of 2-({3-[5-(4-chlorophenyl)-2H-tetrazol-2-yl]propyl}sulfanyl)-1,3-benzoxazole (5c) and 2-({3-[5-(2-chlorophenyl)-2H-tetrazol-2-yl]propyl}sulfanyl)-1,3-benzoxazole (5d) was established by verifying fungal growth in the presence of osmotic protector-sorbitol. The effect of compound 5c or 5d combined with Fluconazole was determined using the checkerboard method. The calculated fractional inhibitory concentration index (FIC) indicated antagonism (FIC >1). Additionally, survival experiments with lepidopteran Galleria mellonella treated with compounds 5c and 5d were performed and demonstrated the lack of toxicity of these compounds.

Hydroxide derivatives of tetrazole: computational design approach for high-energy materials

Based on the backbone of the nitrogen-rich triazole and tetrazole structure, their N–OH derivatives were designed to improve the properties of energetic materials. This work introduces five novel nitrogen-rich derivatives and their energetic salts as high-performance compounds. Reliable methods and correlations are used to predict the heat of formation, density, detonation, and combustion properties and explosive power. The predicted energetic properties are also compared with well-known explosives, TNT, TATB, RDX, and HMX, to evaluate the performance. A majority of the designed salts exhibited high positive heats of formation, good detonation properties, and high explosive power. Ammonium, hydrazinium, and hydroxylammonium salts (1–3), which have relatively high densities (over 1.86 g/cm3), resulted in good detonation velocities (above 9.0 km/s) and pressures (above 35 GPa), making them competitive energetic materials.

Near-Infrared Photoinduced Coupling Reactions Assisted by Upconversion Nanoparticles.

We introduce nitrile imine-mediated tetrazole-ene cycloadditions (NITEC) in the presence of upconversion nanoparticles (UCNPs) as a powerful covalent coupling tool. When a pyrene aryl tetrazole derivative (λabs, max =346 nm) and UCNPs are irradiated with near-infrared light at 974 nm, rapid conversion of the tetrazole into a reactive nitrile imine occurs. In the presence of an electron-deficient double bond, quantitative conversion into a pyrazoline cycloadduct is observed under ambient conditions. The combination of NITEC and UCNP technology is used for small-molecule cycloadditions, polymer end-group modification, and the formation of block copolymers from functional macromolecular precursors, constituting the first example of a NIR-induced cycloaddition. To show the potential for in vivo applications, through-tissue experiments with a biologically relevant biotin species were carried out. Quantitative cycloadditions and retention of the biological activity of the biotin units are possible at 974 nm irradiation.

Synthesis and Identification of Some New Tetrazole Derivatives from 4,5-dichloro Imidazole and Study of Their Biological Activity

Synthesis and Identification of Some New Tetrazole Derivatives from 4,5-dichloro Imidazole and Study of Their Biological Activity

ChemInform Abstract: Metal‐Free Tandem Oxidative Coupling of Primary Alcohols with Azoles for the Synthesis of Hemiaminal Ethers.

AbstractThe protocol is successfully applied to various benzotriazole, tetrazole, carbazole, and indazole derivatives, but fails upon the transformation of indole or benzodiazole derivatives.

Synthesis of polybrominated benzimidazole and benzotriazole derivatives containing a tetrazole ring and their cytotoxic activity.

A series of new benzimidazole and benzotriazole derivatives containing a tetrazole moiety was synthesized by N-alkylation of 5-aryltetrazole with 4,5,6,7-tetrabromo-1-(3-chloropropyl)-1H-benzimidazole and 4,5,6,7-tetrabromo-2-(3-chloropropyl)-2H-benzotriazole. The reaction was regioselective and mostly 2,5-disubstituted tetrazole derivatives were obtained. The effect of all synthesized compounds on human recombinant casein kinase 2alpha subunit (rhCK2α) and cytotoxicity against human T-cell lymphoblast (CCRF-CEM) and breast adenocarcinoma (MCF-7) cell lines were evaluated. The results have shown that many of the synthesized compounds exhibit significant cytotoxicity at micromolar concentration.Graphical abstract

Synthesis, Characterization of Derivatives Tetrazoles for Trimethoprim Drug

The present work involved synthesis of serval new substituted tetrazole via Schiff bases for trimethoprim drug by two steps. The first step involved direct reaction of different ketones and aldehydes with trimethoprim producing the corresponding Schiff bases (1-10), whereas the second step, involved preparation new tetrazoles derivatives (11-20) through reaction of the ready Schiff bases (in the first step) with sodium azidein in dioxin. The prepared compounds were characterized by UV, FT-IR, and some of them by 13C-NMR, 1H-NMR spectroscopy and physical properties.

Design, Synthesis and Biological Evaluation of New Substituted Sulfonamide Tetrazole Derivatives as Antitubercular Agents

AbstractThe 1,2,4 triazole and tetrazole pharmacophore is still considered a viable lead structure for the synthesis of more efficacious and broad spectrum anti‐microbial agents. In this communication, a new class of highly potent anti‐tuberculosis agents are reported. Designed and synthesized a series of 18 compounds and evaluated them for their anti‐tubercular activity against Mycobacterium tuberculosis H37Rv strain. Among the compounds tested, five compounds exhibited moderate anti‐TB activity (MIC = 6.25 µg/mL); compounds 8a, 8d, 8i, 9b and 9f displayed good activity (Minimal inhibition concentration (MIC) = 3.12 µg/mL), while compounds 8e, 8g, 8h, 9d and 9h exhibited excellent activity (MIC = 1.56 µg/mL) against the growth of Mycobacterium tuberculosis H37Rv. Furthermore, they displayed no toxicity against CHO‐K1 cell lines at a concentration of 100 µM. These investigated analogues have emerged as potential leads to extend the scope of the anti‐tubercular research. Additionally, the most active compounds were docked to enzyme MTB CytP51 (2CIB.pdb) to understand ligand‐receptor binding interactions.

Microwave (Mw)‐assisted Synthesis of 5‐Substituted 1H‐Tetrazoles via [3+2] Cycloaddition Catalyzed by Mw‐Pd/Co Nanoparticles Decorated on Multi‐Walled Carbon Nanotubes

AbstractMonodisperse Pd/Co nanoparticles (Mw−Pd/Co@CNT NPs) decorated multi‐walled carbon nanotubes have been reproducibly and easily synthesized by microwave assisted method. They were found to be remarkable catalysts for the preparation of tetrazole derivatives which have significant benefits in wide range of drug purposes. Mw−Pd/Co@CNT NPs were characterized by X‐ray diffraction (XRD), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HR‐TEM) and X‐ray photoelectron spectroscopy (XPS). The results showed the fact that the prepared catalysts are highly crystalline, monodisperse and colloidally stable. The catalytic performance of these NPs was examined for any preparation of tetrazole derivatives and it's found that these Mw−Pd/Co@CNT NPs showed extraordinary catalytic activity, stability and durability. All products were provided with perfect yield in addition to shortest reaction time by employing Mw−Pd/Co@CNT as a heterogeneous catalyst. Our synthesis process comes with a facile and eco‐friendly option to Mw−Pd/Co@CNT, allowing further scrutiny of current catalysts for numerous other chemical reactions.

Crystal Structure and Improved Synthesis of 1‐(2H‐Tetrazol‐5‐yl)guanidium Nitrate

AbstractEnergetic derivatives of tetrazoles are one of the key areas of research focus in pursuit of novel high energy materials, useful as propellants and explosives. Herein, the crystal structure and an improved synthetic procedure of 1‐(2H‐tetrazol‐5‐yl)guanidine (1) and its nitrate salt (2) are reported. The compounds were structurally characterized by spectroscopic (FT‐IR, 1H NMR, 13C NMR) and elemental analysis. The molecular structure of tetrazolyl guanidium nitrate (2) was solved using low temperature single‐crystal X‐ray diffraction. 2 crystallized as its hemihydrate in the orthorhombic space group Fdd2, with a crystal density of 1.69 g cm−3. Thermal behavior and decomposition of the molecules were studied with differential scanning calorimetry (DSC). Molar enthalpy of formation (ΔfHm) of compound 2 was back calculated from heat of combustion (ΔcH0) value obtained experimentally using bomb calorimetric measurements. Lattice enthalpy of 1‐(2H‐tetrazol‐5‐yl)guanidium nitrate was directly calculated from measured crystal density using Jenkins equation. Preliminary ballistic parameters of the compound were predicted and compared with reported high nitrogen tetrazole derivatives.

Indium(III) Chloride Catalyzed Synthesis of 5-Substituted 1H-Tetrazoles from Oximes and Sodium Azide

A simple and efficient protocol has been developed for the synthesis of 5-substituted 1<i>H</i>-tetrazole derivatives in good to excellent yields from various oximes and sodium azide by using indium(III) chloride as a Lewis acid catalyst. The present method has significant advantages, such as an inexpensive catalyst, low catalyst loading, mild reaction conditions, and simple experimental procedures.

An Efficient Protocol for Facile Synthesis of New 5-Substituted-1H-Tetrazole Derivatives Using Copper-Doped Silica Cuprous Sulfate (CDSCS) as Heterogeneous Nano-Catalyst

A facile and highly efficient protocol for synthesis of new 5-substituted-1H-tetrazoles derivatives using copper-doped silica cuprous sulfate (CDSCS) is described. In this method, the cycloaddition reaction of sodium azide with structurally diverse nitriles involving bioactive N-heterocyclic cores exploiting CDSCS in refluxing H2O/i-PrOH (1:1, v/v) furnishes the corresponding 5-substituted-1H-tetrazoles in good to excellent yields (up to 93%). The influence of parameters effective in progress of reaction including solvent type, temperature and catalyst was studied and discussed. In this protocol, CDSCS was proved to be an efficient heterogeneous nano-catalyst to easily achieve the new tetrazole derivatives. The advantages of CDSCS in current protocol known are its cheapness, thermal and chemical stability, ease of recyclability and reusability for several consecutive runs without significant decline in its reactivity.

A Review on New Antihypertensive Agent: Irbesartan

Hypertension is currently measure disorder obtain in the world population. Irbesartan is classified as an angiotensin II receptor type 1 antagonist. Angiotensin II receptor type 1 antagonists are widely used in treatment of diseases like hypertension, heart failure, myocardial infarction and diabetic nephropathy. The clinical and pharmacological analysis of this drug gives idea about effectivity of this drug in hypertension condition. Irbesartan act on renin angiotensin system and decreases biding of angiotensin to the receptor so decreases the blood pressure and act as an antihypertensive agent. Irbesartan is tetrazole derivative which selectively inhibit or antagonise the angiotensin type II receptor. In this review gives detail about mechanism of action of irbesartan in hypertension.

Synthesis, Characterization of Derivatives Tetrazoles for Trimethoprim Drug

The present work involved synthesis of serval new substituted tetrazole via Schiff bases for trimethoprim drug by two steps. The first step involved direct reaction of different ketones and aldehydes with trimethoprim producing the corresponding Schiff bases (1-10), whereas the second step, involved preparation new tetrazoles derivatives (11-20) through reaction of the ready Schiff bases (in the first step) with sodium azidein in dioxin. The prepared compounds were characterized by UV, FT-IR, and some of them by 13C-NMR, 1H-NMR spectroscopy and physical properties.

The first organocopper tetrazole derivative: synthesis and characterization.

1-(5-Amino-3-azapentyl)tetrazole dihydrochloride (HL·2HCl) was prepared by heterocyclization of diethylenetriamine with triethyl orthoformate and sodium azide followed by treatment with potassium carbonate and hydrochloric acid. The reaction of CuCl2, HL·2HCl and triethylamine (NEt3) in a molar ratio of 1 : 1 : 3 in water was found to generate a novel organometallic tetrazole derivative Cu2L2Cl2. This compound is present as a binuclear centrosymmetric molecular complex, in which C-deprotonated tetrazole L acts as a chelating ligand via the two amino N and tetrazole ring C coordination sites and the two copper atoms are linked together through two tetrazole ring N(4)-C(5) bridges. This complex is the first organocopper tetrazole derivative. When the molar ratio of the reagents in the abovementioned reaction was changed to 1 : 2 : 2, the complex Cu(HL)2Cl2 was formed along with Cu2L2Cl2. Pure Cu(HL)2Cl2 was isolated after reaction of the reagents in a molar ratio of 1 : 3 : 6. The complex Cu(HL)2Cl2 is present as a mononuclear molecular complex, with a chelating coordination mode of HL via the two amino N atoms only. Both complexes as well as HL·2HCl were characterized by single-crystal X-ray analysis.

Synthesis and biological evaluation of 3-tetrazolo steroidal analogs: Novel class of 5α-reductase inhibitors

In the present study, a series of steroidal tetrazole derivatives of androstane and pregnane have been prepared in which the tetrazole moiety was appended at C-3 and 17a-aza locations. 3-Tetrazolo-3,5-androstadien-17-one (6), 3-tetrazolo-19-nor-3,5-androstadien-17-one (10), 3-tetrazolo-3,5-pregnadien-20-one (14), 17a-substituted 3-tetrazolo-17a-aza-d-homo-3,5-androstadien-17-one (26–31) and 3-(2-acetyltetrazolo)-17a-aza-d-homo-3,5-androstadien-17-one (32) were synthesized from dehydroepiandrosterone acetate (1) through multiple synthetic steps. Some of the synthesized compounds were evaluated for their in vitro 5α-reductase (5AR) inhibitory activity by measuring the conversion of [3H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity also showed a significant reduction (p <0.05) in rat prostate weight. The most potent compound 14 showed 5AR-2 inhibition with IC50 being 15.6nM as compared to clinically used drug finasteride (40nM). There was also a significant inhibition of 5AR-1 with IC50 547nM compared to finasteride (453nM).

An efficient one-pot protocol for the conversion of benzaldehydes into tetrazole analogs

An efficient protocol has been developed for the one-pot synthesis of tetrazole derivatives in moderate to good yields starting from substituted benzaldehydes and proceeding via non-isolated oxime and nitrile intermediates. The structures of the desired products were confirmed by IR, and NMR spectroscopy as well as mass spectrometry. A plausible reaction mechanism is also discussed.

In vitro pharmacological evaluation of multitarget agents for thromboxane prostanoid receptor antagonism and COX-2 inhibition

PurposePatients with high cardiovascular risk due to ageing and/or comorbidity (diabetes, atherosclerosis) that require effective management of chronic pain may take advantage from new non-steroidal anti-inflammatory drugs (NSAIDs) that at clinical dosages may integrate the anti-inflammatory activity and reduced gastrointestinal side effects of selective cyclooxygenase-2 (COX-2) inhibitor (coxib) with a cardioprotective component involving antagonism of thromboxane A2 prostanoid (TP) receptor. MethodsNew compounds were obtained modulating the structure of the most potent coxib, lumiracoxib, to obtain novel multitarget NSAIDs endowed with balanced coxib and TP receptor antagonist properties. Antagonist activity at TP receptor (pA2) was evaluated for all compounds in human platelets and in an heterologous expression system by measuring prevention of aggregation and Gq-dependent production of intracellular inositol phosphate induced by the stable thromboxane A2 (TXA2) agonist U46619. COX-1 and COX-2 inhibitory activities were assessed in human washed platelets and lympho-monocytes suspension, respectively. COX selectivity was determined from dose–response curves by calculating a ratio (COX-2/COX-1) of IC50 values. ResultsThe tetrazole derivative 18 and the trifluoromethan sulfonamido-isoster 20 were the more active antagonists at TP receptor, preventing human platelet aggregation and intracellular signalling, with pA2 values statistically higher from that of lumiracoxib. Comparative data regarding COX-2/COX-1 selectivity showed that while compounds 18 and 7 were rather potent and selective COX-2 inhibitor, compound 20 was somehow less potent and selective for COX-2. ConclusionThese results indicate that compounds 18 and 20 are two novel combined TP receptor antagonists and COX-2 inhibitors characterized by a fairly balanced COX-2 inhibitor activity and TP receptor antagonism and that they may represent a first optimization of the original structure to improve their multitarget activity.