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Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects millions globally, with increasing urban cases outside of Latin America. Treatment is based on two compounds, namely, benznidazole (BZ) and nifurtimox, but chronic cases pose several challenges. Targeting lysine acetylation, particularly bromodomain-containing proteins, shows promise as a novel antiparasitic target. Our research focuses on TcBDF3, a cytoplasmic protein, which is crucial for parasite differentiation that recognizes acetylated alpha-tubulin. In our previous study, A1B4 was identified as a high-affinity binder of TcBDF3, showing significant trypanocidal activity with low host toxicity in vitro. In this report, the binding of TcBDF3 to A1B4 was validated using differential scanning fluorescence, fluorescence polarization, and molecular modeling, confirming its specific interaction. Additionally, two new 1,3,4-oxadiazoles derived from A1B4 were identified, which exhibited improved trypanocide activity and cytotoxicity profiles. Furthermore, TcBDF3 was classified for the first time as an atypical divergent member of the bromodomain extraterminal family found in protists and plants. These results make TcBDF3 a unique target due to its localization and known functions not shared with higher eukaryotes, which holds promise for Chagas disease treatment. [ABSTRACT FROM AUTHOR]

In this study, a new series of 1,3,4-oxadiazole derivatives (3a– 3h) was synthesized, characterized using various analytical techniques (FT-IR, 1H- and 1 3 C-NMR, mass spectrometry), and tested for their effectiveness against Ehrlich's Ascites Carcinoma (EAC) cell lines in vitro. After 48 h of exposure to these test compounds, the EAC cells exhibited a dose-dependent reduction in their viability. Among the tested compounds, 3b and 3e demonstrated the most potent anticancer effects, with IC 5 0 values of 352.69 μ M and 177.44 μ M, respectively. Consequently, these compounds were chosen for further investigation into their mechanisms of action on EAC cell lines. The assessment included the induction of apoptosis and the analysis of DNA damage, which were evaluated using fluorescence staining and the comet assay. These assessments revealed distinctive apoptotic characteristics such as nuclear fragmentation, cytoplasmic shrinkage and DNA damage. As a result, these compounds hold promise as potential anticancer agents. The study also delved into the binding affinities of these compounds through molecular docking analysis, and the findings showed that compounds 3b and 3e exhibited a strong binding affinity with the receptor Transforming Growth Factor-Beta Receptor I (TGF- β RI) kinase (PDB ID: 1PY5), surpassing the reference compound 5-fluorouracil. Additionally, calculations related to Molecular Mechanics Generalized Born Surface Area (MM-GBSA) indicated favorable free binding energy. The compounds also displayed acceptable ADMET properties. To validate the stability of the bond between compounds 3b and 3e with the 1PY5 receptor, a molecular dynamics simulation lasting 100 ns was carried out. A series of 1,3,4-Oxadiazole derivatives (3a-3h) were synthesized in this study. All the synthesized compounds underwent evaluation for their anticancer activity through various methods including MTT assay, apoptosis analysis, examination of DNA damage, and COMET assay. The molecular docking results indicated that the compounds showed significant binding affinity with the Transforming Growth Factor Beta Receptor I (TGF- β RI) kinase. In silico analyses were conducted for all compounds to assess their safety and efficacy, revealing promising results. [ABSTRACT FROM AUTHOR]

Background: In this work, we have identified heterocyclic derivatives with 1,2,4 oxadiazole scaffold mimicking the functions of tyrosine kinase inhibitors. Fourteen molecules that displayed the best fit were picked from the library of compounds and studied under in-silico and in-vitro conditions. Four compounds were selected for further cytotoxicity and ADME (Absorption, Distribution, Metabolism, Elimination) profiling showing IC50 (from 8– 13 μM) values against EGFR positive cancer cell line (MCF7). Methods: A molecular dynamics simulation study was performed to understand the correlation of non-covalent binding energies with biological activity. The drug-like properties of the selected four compounds (7a, 7b, 7e, and 7m) were evaluated by in-vitro ADME studies. Compounds 7a, 7b , and 7m were the active compounds in the molecular dynamics simulations study. Further, EGFR binding activity was confirmed with EGFRWT and EGFRT790M kinase assay using a luminescence-based method. Results: These compounds (7a, 7b , and 7m) showed activity against EGFRWT and mutant EGFRT790M, exhibiting IC50 values of < 10 and < 50 micromolar, respectively. These compounds also possess moderate aqueous solubility in 40– 70 μg/mL at pH 7.4 and 30– 100 μg/mL at pH 4.0. Further, 7a, 7b , and 7m showed balanced lipophilicity with Log D values ranging from 1– 3. They demonstrated a good correlation in Caco-2 permeability with Apparent permeability (Papp) 1 to 5 × 10− 6 cm/s in comparison with 7e , which was found to be highly lipophilic (Log D > 5) and showed high permeability (Papp 17 × 10− 6 cm/s). Lastly, all these compounds were moderately stable in liver microsomes at alkaline pH with a half-life of 30– 60 min, while at a highly acidic pH (2.0), the compounds were stable up to 15– 20 min. Conclusion: Overall, in-vitro ADME results of these molecules showed good drug-like properties, which are well correlated with the in-silico ADME data, making them ideal for developing an oral drug delivery formulation. Graphical [ABSTRACT FROM AUTHOR]

Development of a new effective drugs with low side effects and definite chemical characteristics needs indentification of bioactive scaffolds for further structural optimization. New synthesized derivatives of 4-hetaryl-5-amino-1-aryl-1H-1,2,3-triazoles and 3H-[1,2,3]triazolo[4,5-b]pyridines were tested for anticancer activity using 60 human tumor cell lines within 9 cancer types. The selective influence of (5-amino-1H-1,2,3-triazol-4-yl)quinazolin-4(3H)-ones: 2-(5-amino-1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)quinazolin-4(3H)-one and 2-(5-amino-1-phenyl-1H-1,2,3-triazol-4-yl)-6-bromoquinazolin-4(3H)-one on ovarian cancer OVCAR-4 cells with growth percentage (GP) = -4.08 and 6.63%, respectively, was found. The derivative 5,7-diamino-3-(3-(trifluoromethyl)phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridine-6-carbonitrile possessed high activity towards lung cancer EKVX cells (GP = 29.14%). The compounds were shown to be less toxic than doxorubicin towards non-tumor human embryonic kidney cells of HEK293 line. Thus, the results of our study confirm the anticancer potential of compounds based on 5-amino-1-aryl-1H-1,2,3-triazoles scaffolds and their fused polycyclic derivatives.

1,3,4-Thiadiazole and oxadiazole hetetocycles are well-known pharmacophore scaffolds, which possess wide possibility for chemical modification and identified diverse pharmacological potential. Such essential and many-sided activities let to consider the mentioned heterocycles as ones of the crucial for expression of pharmacological activity, which confirm their importance for medicinal chemistry. Moreover, 1,3,4-oxadiazole cycle is a bioisostere for carboxylic, amide and ester groups, which mostly contribute to enhancement the pharmacological activity by participating in hydrogen bonding interactions with different enzymes and receptors. The aim of the work was analysis of literature data about biological activity of non-condensed heterocyclic systems based on 1,3,4-thia(oxa)diazole rings as promising objects for modern bioorganic and medicinal chemistry. In this study are presented the analysis of actual literature data about pharmacological activity of heterocyclic systems based on 1,3,4-thiadiazole. It has been established that mentioned scaffolds were identified as the main structural component of biological agents with antimicrobial, anti-inflammatory, analgetic, antitumor antitubercular and antiviral activity. Moreover, the combination of 1,3,4-thiadiazole or 1,3,4-oxadiazole core with various heterocycles led to synergistic effect in many cases. Thus, mentioned scaffolds are important heterocyclic fragments that are considered as promising structural matrices for the construction of new drug-likes molecules. An analysis of the biological activity of 1,3,4-thia(oxa)diazole derivatives was carried out, which allowed to confirm their versatile pharmacological potential. Obtained data can be considered as background for further in-depth studies of chemical and pharmacological properties such heterocyclic systems with possible application in medicine.

The present work aims to synthesize 2,5-disubstituted-1,3,4-oxadiazoles using electrochemically prepared nanoparticles of nickel oxide as catalyst. The nanoparticles thus prepared using electrochemical syntheses are in appreciable yield. The tetrabutyl phosphonium bromide has been used for capping followed by UV, FTIR, XRD, SEM EDS and TEM SAED studies for the characterization. The 2,5-disubstituted-1,3,4-oxadiazoles were synthesized from substituted benzoic acids and their hydrazides in microwave synthesis system using prepared nanoparticles as a catalyst. [ABSTRACT FROM AUTHOR]

A series of new 1,3,4-oxadiazoles conjugated to aromatic substituents by an azo linker was synthesized in a four-step reaction sequence, involving cyclodehydration of a N, N'-diacylhydrazine fragment and dehydrogenation of the neighboring hydrazine fragment of the intermediate N, N'-diarylcarbonohydrazide. [ABSTRACT FROM AUTHOR]

A series of diethyl-2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate derivative coupled to 1,3,4-oxadiazole- 5-thiones and 1,2,4-triazole-5-thiones moieties at C2,C6 positions of 1,4-dihydropyridine ring system was prepared. This linkage was carried out by the reaction of 1,3,4-oxadiazole-5-thiones and 1,2,4-triazole-5-thiones with 2,6-dibromomethyl-3,5-diethoxycarbonyl-4-phenyl-1,4-dihydropyridine in the presence of potassium carbonate as a weak base and dry acetone as the solvent. The newly synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR spectral data, elemental analysis and FAB-MS. The synthesized compounds were tested for their antimicrobial and antifungal activity against Escherichia coli and Aspergillus fumigatus in vitro in comparison with Enrofloxacin and Amphotericin as the reference drugs which are normally used for treating such infections. The synthetic compounds showed different inhibition zones against tested bacteria and fungi. Compound 8d showed more antagonistic activity against E. coli and A. fumigatus. [ABSTRACT FROM AUTHOR]

An unprecedented and highly efficient tris(dimethylamino)phosphine [P(NMe2)3]-mediated deoxygenative [4 + 1] annulation of N-acyldiazenes with α-dicarbonyl compounds such as isatins, α-keto esters, and α-diketones is reported. The annulation reactions proceed smoothly under mild conditions to deliver a broad range of 2,2,5-trisubstituted 1,3,4-oxadiazole derivatives in moderate to excellent yields from readily available starting materials. It represents the first realization of the [4+1] annulation mode involving N-acyldiazenes to construct five-membered heterocycles. [ABSTRACT FROM AUTHOR]

ABSTRACT In this paper the synthesis of some substituted 2-dibenzyl 1,3,4-oxadiazole, thiadiazole and 1,2,4-triazoles derived from dibenzyl amine is reported scheme-1. Dibenzyl amine was treated with chloroacetic acid to give N,N –dibenzyl glycine (1) which was converted to its methyl/ ethyl esters (2,3) .The esters were treated with hydrazine hydrate in ethanol to give hydrazide (4)which was reacted with ammounium thiocyanate to give thiosemicarbazide(5).Treatment of thiosemicarbazid(5)with concentrated sulfuric acid , hydrazine hydrate, 4% sodium hydroxide and with potassium iodide / iodine to gave substituted 1,3,4-thiadiazole (6) 1,2,4- triazole (7) 1,2,4-triazole -3-thiol (8) and 5-amino1,3,4-oxadiazole (9) respectively. The acid (1) was treated with polyphosphoric acid and hydrazine hydrate to give 2,5- disubstituted oxadiazole (10), sulfonation of (10) gave disubstituted 1,3,4- thiadiazole (11). Hydrazides (4) was treated with acid chlorides to give thediketones (12-14) which cyclized to substituted oxadiazoles (15-17) and thiadiazoles (18-20) by their reaction with phosphorus pentoxideand phosphorus pentasulfide respectively.Some of the synthesized compounds were tested against various types of bacteria. The structures of the synthesized compounds were confirmed by physical and spectral methods.

The metal-catalyzed cycloaddition of silyl nitronates and nitriles leading to 1,2,4-oxadiazoles is described. Silver(I) triflate (AgOTf) and and ytterbium(III) triflate [Yb(OTf)3] are suitable catalysts. A variety of functional groups is tolerated in the nitrile. The reaction works well for alkenyl and aryl silyl nitronates while the use of alkyl silyl nitronates is less efficient. Mechanistic studies are in favour of an elimination of tert-butyl(dimethyl)silanol (TBSOH) after the cycloaddition step. The new approach has also been applied for the synthesis of the drug ataluren. [ABSTRACT FROM AUTHOR]

A direct C-5-H arylation of 3-substituted 1,2,4-oxadiazoles with aryl iodides in the presence of a palladium catalyst and silver acetate is reported. This method provides a rapid, reliable way to obtain versatile 3,5-diaryl-1,2,4-oxadiazole derivatives, which are common moieties of many biologically active molecules. The synthetic applications of this novel method have been demonstrated in the concise syntheses of Ataluren and a potent RET inhibitor Yhhu251. [ABSTRACT FROM AUTHOR]

A facile stepwise synthesis of 2,5-disubstituted 1,3,4-oxadiazoles proceeding via oxidative cyclization of N-acylhydrazones is reported. The reaction is efficiently promoted by 2,3-dichloro-5,6-dicyano-1,4- benzoquinone (DDQ) to afford the desired products mostly in high yields and in relatively short times. The final 1,3,4-oxadiazole derivatives are also synthesized directly from acid hydrazides and aldehydes in a one-pot procedure. The substrate scope and limitations of the reported transformation are discussed in detail. [ABSTRACT FROM AUTHOR]

The thermolysis of geminal diazides derived from acylacetate compounds is an efficient tool for the rapid construction of the 1,3,4-oxadiazole core. While a broad range of ethyl esters undergoes smooth transformation to the desired heterocycles that contain the ester moiety in moderate to high yields, the analogous tert-butyl esters give rise to the oxadiazoles with acyl groups, presumably through a pathway of decarboxylation followed by a new acyl transfer. [ABSTRACT FROM AUTHOR]

ABSTRACT In this paper the synthesis of some 2-(3-pyridyl)-5-aryl-1,3,4-oxadiazoles from hydrazones is reported. Nicotinic acid was converted to ethyl nicotinate (1) by its reaction with thionyl chloride and the resultant acid chloride was treated with absolute ethanol, the ethyl nicotinates was treated with hydrazine hydrate in ethanol to give the corresponding acid hydrazide (2). The acid hydrazide was treated with benzaldehyde or substituted benzaldehyde to give the hydrazones (3-8). The hydrazones were cyclized to 2-(3-pyridyl)-5-aryl-1,3,4-oxadiazoles (4-14) by their reaction with lead oxide. The structure of the synthesised compounds were confirmed by physical and spectral methods.

ABSTRACT In this paper the synthesis of some substituted 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles was achieved. 2-(2,3-dimethyl phenyl amino) benzoic acid was esterified to its ethyl ester by its reaction with absolute ethanol in presence of concentrated sulfuric acid. The ethyl ester was treated with hydrazine hydrate in ethanol to give the corresponding hydrazide. The hydrazide was converted to substituted thiosemicarbazide by its reaction with ammonium thiocyanate. The thiosemicarbazide was treated with sodium hydroxide solution and with sulfuric acid to give 5-(2,3-dimethyl phenyl amino phenyl)-1,2,4-triazole-3-thiol and 2-(2,3-dimethyl phenyl amino phenyl)-5-amino-1,3,4-thiadiazole respectively. The acid hydrazide was treated with substituted benzaldehyde to give hydrazones which cyclized to disubstituted 1,3,4-oxadiazole, while the reaction of hydrazide with formic acid followed by cyclization of formyl hydrazine by PbO2 to give monosubstituted 1,3,4-oxadiazole. Finally, treatment of hydrazide with carbon disulfite in alcoholic potassium hydroxide gave 2-(2,3-dimethyl phenyl amino phenyl)-1,3,4-oxadiazole-5-thiol. The structures of the synthesized compounds were confirmed by physical and spectral means.

ABSTRACT In this paper the synthesis of some substituted 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles is reported. Ethyl methacrylate was treated with hydrazine hydrate in ethanol to give the corresponding hydrazide (1). The hydrazide was converted to 1-acyl thiosemicarbazide (2) byits reaction with ammonium thiocyanate, which was treated with sodium hydroxide solution and with concentrated sulfuric acid to give 5-substituted-1,2,4-triazoles-3-thiol (3) and 2-substituted-5-amino-1,3,4-thiadiazole (4) respectively. The acid hydrazide (1) was treated with benzaldehyde or substituted benzaldehyde to give hydrazones (7-12), the hydrazones were then cyclized with lead dioxide to 2-subtituted-5-phenyl 1,3,4-oxadiazole (14). The reaction of the hydrazide (1) with formic acid gave 1-formyl-2-acyl hydrazine (6) and the cyclization of (6) by phosphorus pentaoxide gave monosubstituted-1,3,4-oxadiazoles (13). Acid hydrazide (1) was treated with phenyl isothiocyanate to give substituted thiosemicarbazide (5).

The clean cyclization of chalcones (1a–c/2a–c) with hydrazine hydrate under microwave irradiation afforded pyrazolines derivatised with sydnone (3d–i/4d–i), which underwent 1,3-dipolar cyclo-addition with acetic anhydride to form pyrazolines appended with 1,3,4-oxadiazoles (5g–l/6g–l). The newly synthesized compounds were confirmed by spectral and elemental analyses. In comparison to classical heating, the results indicate that microwave irradiation affords higher yields, shorter reaction times (4–12 min) and cleaner reactions.

A one-step, simple and straightforward synthesis of the title amides from the corresponding carboxylic acids, urea and imidazole under microwave irradiation is described.

Herein, we report the first Cu-catalyzed one-step method for the synthesis of 1,2,4-oxadiazoles from stable, less toxic, and readily available amides and organic nitriles by a rare oxidative N-O bond formation using O2 as sole oxidant. This method has a broad substrate scope and a good tolerance for diverse functional groups. Moreover, the synthetic utility of this method is highlighted by the synthesis of biologically active 3,5-disubstituted derivatives. [ABSTRACT FROM AUTHOR]

The known oxadiazoles 3,5-bis-(phenyl)-1,2,4-oxadiazole (3a); the 3-(4-chlorophenyl)-5-phenyl-1,2,4-oxadiazole (3b); and the new 3,5-diphenylchlorinated-1,2,4-oxadiazoles 3c-e were synthesized from the reaction of benzamidoximes with an appropriated acid chloride and cyclisation of the resulting O-acylbenzamidoxime intermediate. The compounds synthesized were characterized on the basis of their IR, NMR (1D and 2D) and mass spectral data. Compounds 3a-e were evaluated for their antimicrobial activity and for their toxicity towards brineshrimp (Artemia salina Leach). Os oxadiazóis 3,5-bis-(fenil)-1,2,4- oxadiazol (3a) e 3-(4-clorofenil)-5-fenil-1,2,4-oxadiazol (3b), já descritos na literatura, e, os 1,2,4- oxadiazóis-3,5-fenilclorados inéditos 3c-e, foram sintetizados pela reação de bezamidoximas com um cloreto de ácido apropriado, seguido da ciclização do intermediário O-acilíco resultante. Os compostos obtidos foram caracterizados com base nas análises dos dados espectroscópicos de IV, EM e RMN (uni- e bidimensionais). Os compostos 3a-e foram submetidos a bioensaios paraavaliação de atividade antimicrobiana e, de toxicidade frente ao microcrustáceo Artemia salina Leach.

5-Furan-2-yl[1,3,4]oxadiazole-2-thiol (Ia) and 5-furan-2-yl-4H-[1,2,4]-triazole-3-thiol (Ib) were synthesized from furan-2-carboxylic acid hydrazide. Mannich basesand methyl derivatives were then prepared. The structures of the synthesized compoundswere confirmed by elemental analyses, IR and 1H-NMR spectra. Their thiol-thione tautomericequilibrium is described.

The 6-aryl-1-(3-chloropropanoyl)-4-[(E)-1-(2-furyl)methylidene)]-1,2,3,4-tetrahydro-3-pyridazinones (6a-d) were synthesized by the reaction of acid chloride 3 with α-aracyl(β-2-furyl)acrylic acid hydrazides (2a-d) in a high yield, one pot reaction. On the other hand, 2-(2-chloroethyl)-5-[α-aracyl-β-(2-furyl)]-(E)-vinyl-1,3,4-oxadiazoles (7a-d) were also prepared by cyclodehydration of N1[α-aracyl-β-(2-furyl)acroyl-N2[3-chloro-propanoyl] hydrazine derivatives (4a-d). The proposed structures of the products were confirmed by elemental analysis, spectral data and chemical evidence.

An efficient cyclization between nitro-substituted benzoic acids and nitro-substituted benzohydrazides affords 1,3,4-oxadiazoles. Facile synthesis and a broad substrate scope produce a range of compounds, some of them with potential as high-energy compounds. Heats of formation (Δ Hf) and densities ( ρ) were calculated, and heats of decomposition (Δ Hd) and combustion (Δ Hc) were determined experimentally. The densities of seven of the synthesized compounds were determined by gas pycnometry, and the respective values of detonation velocity ( VD), detonation pressure ( PD) and specific impulse ( ISP) were calculated using the EXPLO5 program. An X-ray structure of 2-(2,4-dinitrophenyl)-5-(3,5-dinitrophenyl)-1,3,4-oxadiazole ( 4n) revealed the non-planarity of the molecule and afforded a crystal density of 1.698 (at 120 K), close to the pycnometric value of 1.64 at room temperature. [ABSTRACT FROM AUTHOR]

A series of new 2,5-disubstituted 1,3,4-oxadiazoles was synthesized under conventional thermal heating and microwave irradiation conditions through the reaction of acyl hydrazides with Nprotected α-amino acid in presence of a small amount of POCl3. Heterocycles were obtained in moderate to good yields and in relatively short reaction times. [ABSTRACT FROM AUTHOR]

New symmetrically substituted derivatives of 2,5-bis(4-arylphenyl)-1,3,4-oxadiazole were prepared from 2,5-bis(4-bromophenyl)-1,3,4-oxadiazole and various thiophene-, furan-, pyridine- or benzene-containing boronic acids by a palladium catalyzed Suzuki cross-coupling reaction under the conditions of the phase transfer catalysis. The structure of the products, the absorption and emission spectra and their electrochemistry were also studied. [ABSTRACT FROM AUTHOR]

Rapid and highly efficient synthesis of 2- or 2,5-substituted 1,3,4-oxadiazoles by the condensation of aryl carboxylic acid hydrazides and orthoesters can be achieved under microwave irradiation using an unmodified commercial over in unsealed vessels.

A safe and facile method for the formation of 3-trifluoromethyl-5-amino-1,2,4-oxadiazoles, via a reversed addition of hydroxylamine to cyanamides, is reported. This two-pot procedure is suitable to scale-up and avoids the hazards associated with trifluoromethyl amidoxime synthesis. [ABSTRACT FROM AUTHOR]

In the described research work, a new series of N-substituted derivatives of 5-(4- chlorophenyl)-1,3,4-Oxadiazol-2-yl-2-sulfanyl acetamide has been synthesized. The synthesis was carried out by converting 4-chlorobenzoic acid (1) into ethyl 4-chlorobenzoate (2), 4- chlorobenzohydrazide (3) and then 5-(4-chlorophenyl)-1,3,4-Oxadiazol-2-thiol (4) respectively. The target molecules 6a-o were synthesized by reacting compound 4 with different N-alkyl/aryl substituted 2-bromoacetamide (5a-o) in equimolar ratios of using DMF and sodium hydride (NaH). The structure of all the synthesized compounds was confirmed by spectral data like EI-MS, IR and 1H-NMR. The compounds were also analysed for antimicrobial & hemolytic activity and most of them were found active against the selected microbial species at variable extent relative to reference standards. But 6f and 6o were the active against the selected panel of microbes and former was most potent one. This series revealed less toxicity and may consider for further biological screening and application trial except 6g and 6j, exhibiting high cytotoxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] Continuing on our antiviral drug discovery research, we intended to diversify our lead anti-HIV-1 inhibitor by non-classical isosteric replacement of amide to 1,2,4-oxadiazoles. The resulting molecules isoxazole-1,2,4-oxadiazole analogs were synthesized using mild bases in ethanol under microwave irradiation. The anti-HIV potential was checked in human CD4+ reporter cell lines, TZM-bl and CEM-GFP, at the highest non-cytotoxic concentration (HNC), demonstrating that 3-((3-(p-tolyl)isoxazol-5-yl)methyl)-1,2,4-oxadiazole and 3-((3-(4-chlorophenyl)isoxazol-5-yl)methyl)-1,2,4-oxadiazole inhibit HIV-1 replication significantly and could be considered as a new lead candidate against HIV-1. [ABSTRACT FROM AUTHOR]

Background Taking into account the improvement in insecticidal activity by the inclusion of fluorine in the hydrazone moiety, the authors synthesized new 4-fluorobenzoic acid hydrazides and 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles, substituting a phenyl group or a heteroaryl ring carrying one or two atoms of F, Cl and Br, and investigated their biting deterrent and larvicidal activities against Aedes aegypti for the first time. Results The compound 3-acetyl-5-(4-fluorophenyl)-2-[4-(dimethylamino)phenyl]-2,3-dihydro-1,3,4-oxadiazole (17) produced the highest biting deterrent activity ( BDI = 1.025) against Ae. Aegypti, followed by 4-fluorobenzoic acid [(phenyl)methylene] hydrazide (1). These activity results were similar to those of N, N-diethyl- meta-toluamide ( DEET), which showed a proportion not biting of 0.8-0.92. When compounds 1 and 17 were tested on cloth worn on human volunteers, compound 1 was not repellent for some volunteers until present in excess of 500 nmol cm−2, while compound 17 was not repellent at the highest concentration tested (1685 nmol cm−2). In the larvicidal screening bioassays, only compounds 10, 11, 12 and 17 showed 100% mortality at the highest screening dose of 100 ppm against Ae. aegypti larvae. Compounds 11 and 12 with LD50 values of 24.1 and 30.9 ppm showed significantly higher mortality than 10 (80.3 ppm) and 17 (58.7 ppm) at 24-h post-treatment. Conclusion The insecticidal and biting deterrent activities were correlated with the presence of a halogen atom on the phenyl or heteroaryl substituent of the hydrazone moiety. [ABSTRACT FROM AUTHOR]

The reaction of adamantane-1-carbohydrazide (1) with heterocyclic aldehydes, namely 5-(4-chlorophenyl)isoxazole-3-carboxaldehyde (2a), 5-(4-methylphenyl)isoxazole- 3-carboxaldehyde (2b), 5-(4-methoxyphenyl)isoxazole-3-carboxaldehyde (2c), 1H-imidazole-2-carboxaldehyde and 2-butyl-4-chloro-1H-imidazole-5-carboxaldehyde, in ethanol, yielded the corresponding N′-heteroarylidene-1-adamantylcarbohydrazides 3a, 3b, 3c, 4 and 5, respectively, in good yields. The 4-acetyl-1,3,4-oxadiazoline analogues 6a-c were prepared in 48-55% yields by heating their corresponding N′-heteroarylidene-1- adamantylcarbohydrazides 3a-c with acetic anhydride for two hours. Compounds 3a-c, 4, 5 and 6a-c were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 4 and 5 displayed potent broad-spectrum antimicrobial activity, while compounds 3a-c showed good activity against the Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

The reaction of p-bromoanilino acetohydrazide(II) with aromatic aldehydes in alcohol yielded 2-[4-bromo aniline] N-substituted benzylidine hydrazides (IIIa-IIIj), which in presence of yellow mercuric oxide and iodine in DMF, yielded corresponding 4-bromo[(N-5-substituted 1,3,4 oxadiazole-2 -yl)methyl]aniline (IVa-IVj). Structures of the compounds synthesized were confirmed by IR, ¹HNMR and MASS spectroscopic analysis. The newly synthesized compounds were screened for antibacterial, antifungal and anti-inflammatory activities. Some of the compounds showed remarkable antibacterial, antifungal and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

In search for a better anticonvulsant drug and the importance of semicarbazones and 2,5-disubstituted 1,3,4-oxadiazoles as anticonvulsant pharmacophore, a series of novel substituted semicarbazones were designed, synthesized, and evaluated for their anticonvulsant activity. The chemical structures of the synthesized molecules were confirmed by elemental and spectral (IR, H NMR, C NMR and MS) analysis. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure and subcutaneous pentylenetetrazole ( scPTZ) models. Efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present study validated that the pharmacophore model with four binding sites is essential for anticonvulsant activity. [ABSTRACT FROM AUTHOR]

Two ferrocenyl-substituted 1,3,4-oxadiazoles, 2-ferrocenyl-1,3,4-oxadiazole (1) and 2,5-diferrocenyl-1,3,4-oxadiazole (2), have been prepared from the corresponding hydrazides, (ferrocenecarbonyl)hydrazine (3) and 1,2-bis(ferrocenecarbonyl)hydrazine (4), and characterized by conventional spectroscopic methods (IR, NMR, MS) and elemental analyses. The solid-state structures of 1, 2 and 4 have been determined by single-crystal X-ray diffraction analysis. The redox behavior of 1 and 2 was studied by electrochemical methods. Compound 1 underwent a reversible one-electron oxidation attributed to the ferrocene/ferrocenium couple (Eo′ = +0.28 V vs ferrocene/ferrocenium). On the other hand, compound 2 showed two closely separated anodic waves corresponding to two consecutive redox changes, indicating some degree of electronic communication between the ferrocenyl moieties in positions 2 and 5 at the 1,3,4-oxadiazole ring. [ABSTRACT FROM AUTHOR]

The acid hydrolysis of a series of 5-aryl-3-(β-thiomorpholinoethyl)-1,2,4-oxadiazoles gave substituted benzoic acids and 2-amino-8-thia-1-aza-5-azoniaspiro[4.5]dec-1-ene chloride hydrate, whose structure was demonstrated by spectral methods and X-ray diffraction structural analysis. [ABSTRACT FROM AUTHOR]

Fatty acid hydrazides of undec-10-enoic, ( Z)-octadec-9-enoic, ( Z)-12-hydroxyoctadec-9-enoic and ( Z)-9-hydroxyoctadec-12-enoic acids are used as cheap starting materials in the synthesis of important biologically active 5-(alkenyl)-2-amino-1,3,4-oxadiazole and 2-(alkenyl)-5-phenyl-1,3,4-oxadiazole using cyanogen bromide and benzoyl chloride or benzoic acid as reagents, respectively. The structure of these compounds was confirmed by IR, 1H NMR, 13C NMR and Mass spectra. All the newly synthesized compounds were screened for their antibacterial activity. Compounds 2c, 2d, 3a, 3c and 3d showed good antimicrobial activity against E. coli where as compounds 2a and 2d were found active against all the bacteria. [ABSTRACT FROM AUTHOR]

A series of structurally similar 1, 3, 4-oxadiazoles with enzyme tyrosinase inhibitor activity have been subjected for QSAR analysis using V life MDS 3.5 software. The compounds were divided into training and test set. Best QSAR models were selected on the basis of various statistical parameters like square correlation coefficient (r²), cross validated square correlation coefficient (q²), standard error of estimation (SE) and sequential Fischer test (F). 2D QSAR study reveals that tyrosinase inhibitor activity is governed by Alignment Independent (AI) descriptors whereas as per 3D QSAR studies a new compounds, with more electronegative and less bulky substituent, from this series could have better tyrosinase inhibitor activity. [ABSTRACT FROM AUTHOR]

4,5-Dihydro-1,2,4-oxadiazoles were prepared using 1,3-dipolar cycloaddition of imines with nitrile oxides. Further reductive N-O bond cleavage furnished monosubstituted N-aryl amidines in good yield. Thus an efficient route for the synthesis of monosubstituted N-aryl amidines has been developed. [ABSTRACT FROM AUTHOR]

Abstract: Ultrasound irradiation, an efficient and innocuous technique of reagent activation for synthesizing organic compounds, has been applied with success to transform seven carboxylic acids to fourteen secondary amides in good to excellent yields. The reaction has worked well either with aryl or alkyl carboxylic acids as well as with aromatic or aliphatic amines. This methodology is expeditious and reliable for preparing secondary carboxamides which in many cases are embedded in the C-5 side-chain of 1,2,4-oxadiazoles (14, 15, 17–27). The elemental analyses of new compounds (19–27) in conjunction with the spectral data of all synthesized amides gave an idea about their structures, while the crystallographic data of one of the compounds (26) supplied information concerning the configurational behavior of the amidic part and also the conformational aspect of the entire molecule in the crystalline state. [Copyright &y& Elsevier]

The article discusses the study which explores synthesis and antifungal activity of 2-azetidinonyl-5 methyl oxadiazoles against seed-borne pathogens of Eleusine coracana in benzophenone. The study shows a simple high-yielding method for the integration of heterocyclic rings at the benzophenone nucleus on a wet solid surface with the use of microwave irradiation. It concludes that synthesized compounds have effects in depleting the incidence of seed-borne pathogenic fungi or finger millet.

A series of novel 3,5-disubstituted-1,2,4-oxadiazoles have been synthesized utilizing either long-chain alkenoates or acyl chlorides with amidoximes in presence of base. The structures of the synthesized compounds were elucidated by IR, mass, 1H and 13C NMR spectroscopy and elemental analysis. [ABSTRACT FROM AUTHOR]

The synthesis and liquid crystalline properties of novel achiral amides (Ia-g, IIa-g and IVa,b), achiral Schiff's bases (IIIa-g and Va-g), chiral amides (VI, VII) and chiral Schiff's bases (VIII-XI) incorporating a 1,3,4-oxadiazole ring are reported. All amides of the series I and II display an enantiotropic smectic A phase. The amide IVa,b did not show mesomorphic properties. Amides of the series Ia-g and IIa-g contain a flexible n-tetradecylthio chain, the other terminal substituent is an n-alkoxy chain and n-alkyl chain, respectively (n = 4-10) and the 1,3,4-oxadiazole is in the terminal rigid core. Amides Ia-g have broader mesomorphic range and higher thermal stability than the corresponding amides IIa-g. Amides IVa,d contain the 1,3,4-oxadiazole ring in the centre of the rigid core and two flexible alkoxy chains as flexible terminal substituents. Thus, the mesomorphic properties are favoured if 1,3,4-oxadiazole is shifted to a terminal position of the rigid core. Schiff's bases IIIa-g display an enantiotropic dimorphism smectic C-smectic A. Schiff's bases IIIa-g have a broader mesomorphic range than the analogous amides Ia-g. Schiff's bases Va-g exhibit a dimorphism smectic A-nematic, and in contrast to this the analogous amide IVa,b did not show mesomorphism. The chiral amides VI and VII and chiral Schiff's bases X and XI did not show mesomorphic properties and only the chiral Schiff's bases VIII and IX display a chiral smectic C phase in a short mesomorphic range. A density functional theory theoretical study at the B3LYP/6-311++G(d,p) level was performed in order to analyse the structural features that must be related with the mesomorphic behaviour of the reported compounds. [ABSTRACT FROM AUTHOR]