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Herein we report the synthesis of (E)-3-aryl-2-(5-aryl-4H-1,2,4-triazol-3-yl)acrylonitriles 3 a–k whose fluorescence properties have been investigated for the first time. A plausible reaction mechanism has been proposed to explain the total observed stereospecific formation of the E-isomers of compounds 3 a–k. The fluorescence analysis of compounds 3a-f has revealed relatively low values of the fluorescence emission quantum yields in a range of ∼1 to 10 %, depending in the nature of the substituents.

Toxicity and resistance to newly synthesized anticancer drugs represent a challenging phenomenon of intensified concern arising from variation in drug targets and consequently the prevalence of the latter concern requires further research. The current research reports the design, synthesis, and anticancer activity of new 1,2,3-triazole-coumarin-glycosyl hybrids and their 1,2,4-triazole thioglycosides as well as acyclic analogs. The cytotoxic activity of the synthesized products was studied against a panel of human cancer cell lines. Compounds 8, 10, 16 and 21 resulted in higher activities against different human cancer cells. The impact of the hybrid derivative 10 upon different apoptotic protein markers, including cytochrome c, Bcl-2, Bax, and caspase-7 along with its effect on the cell cycle was investigated. It revealed a mitochondria-apoptotic effect on MCF-7 cells and had the ability to upregulate pro-apoptotic Bax protein and downregulate anti-apoptotic Bcl-2 protein and thus implies the apoptotic fate of the cells. Furthermore, the inhibitory activities against EGFR, VEGFR-2 and CDK-2/cyclin A2 kinases for 8, 10 and 21 were studied to detect the mechanism of their high potency. The coumarin-triazole-glycosyl hybrids 8 and 10 illustrated excellent broad inhibitory activity (IC50= 0.22 ± 0.01, 0.93 ± 0.42 and 0.24 ± 0.20 μM, respectively, for compound 8), (IC50 = 0.12 ± 0.50, 0.79 ± 0.14 and 0.15± 0. 60 μM, respectively, for compound 10), in comparison with the reference drugs, erlotinib, sorafenib and roscovitine (IC50 = 0.18 ± 0.05, 1.58 ± 0.11 and 0.46 ± 0.30 μM, respectively). In addition, the docking study was simulated to afford better rationalization and put insight into the binding affinity between the promising derivatives and their targeted enzymes and that might be used as an optimum lead for further modification in the anticancer field.

In this study, an efficient multistep synthesis of novel aromatic tricyclic hybrids incorporating different biological active moieties, such as 1,3,4-thiadiazole and 1,2,4-triazole, was reported. These target scaffolds are characterized by having terminal lipophilic or hydrophilic parts, and their structures are confirmed by different spectroscopic methods. Further, the cytotoxic activities of the newly synthesized compounds were evaluated using in vitro MTT cytotoxicity screening assay against three different cell lines, including HepG-2, MCF-7, and HCT-116, compared with the reference drug Taxol. The results showed variable performance against cancer cell lines, exhibiting MCF-7 and HepG-2 selectivities by active analogs. Among these derivatives, 1,2,4-triazoles 11 and 13 and 1,3,4-thiadiazole 18 were found to be the most potent compounds against MCF-7 and HepG-2 cancer cells. Moreover, structure–activity relationship (SAR) studies led to the identification of some potent LSD1 inhibitors. The tested compounds showed good LSD1 inhibitory activities, with an IC50 range of 0.04–1.5 μM. Compounds 27, 23, and 22 were found to be the most active analogs with IC50 values of 0.046, 0.065, and 0.074 μM, respectively. In addition, they exhibited prominent selectivity against a MAO target with apparent cancer cell apoptosis, resulting in DNA fragmentation. This research provides some new aromatic-centered 1,2,4-triazole-3-thione and 1,3,4-thiadiazole analogs as highly effective anticancer agents with good LSD1 target selectivity.

Viruses have been recognized as the etiological agents responsible for many pathological conditions ranging from asymptomatic infections to serious diseases, even leading to death. For this reason, many efforts have been made to identify selective viral targets with the aim of developing efficient therapeutic strategies, devoid of drug-resistance issues. Considering their crucial role in the viral life cycle, polymerases are very attractive targets. Among the classes of compounds explored as viral polymerases inhibitors, here we present an overview of non-nucleoside triazole-based compounds identified in the last fifteen years. Furthermore, the structure-activity relationships (SAR) of the different chemical entities are described in order to highlight the key chemical features required for the development of effective antiviral agents.

The synthesis of novel fluoroquinolones, congeners of ciprofloxacin, which was inspired by earlier work on spirocyclic ciprofloxacin, is described. An antibacterial evaluation of the 11 fluoroquinolone compounds synthesized against the ESKAPE panel of pathogens in comparison with ciprofloxacin revealed that the more compact spirocycles in the fluoroquinolone periphery resulted in active compounds, while larger congeners gave compounds that displayed no activity at all. In the active cohort, the level of potency was comparable to that of ciprofloxacin. However, the spectrum of antibacterial activity was quite different, as the new compounds showed no activity against Pseudomonas aeruginosa. Among the prepared and tested compounds, the broadest range of activity (five pathogens of the six in the ESKAPE panel) and the highest level of activity were demonstrated by 1-yclopropyl-7-[8-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-6-azaspiro[3.4]oct-6-yl]-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which is the lead compound nominated for further characterization and development.

Human microsomal prostaglandin E synthase (mPGES)-1 is a glutathione-dependent membrane-bound enzyme which is involved in the terminal stage of prostaglandin E2 (PGE2) synthesis. It has been well reported as a key target for the discovery of new anti-inflammatory and anti-cancer drugs. Specific in- hibitors of mPGES-1 are anticipated to selectively restrain the generation of PGE2 induced by the in- flammatory stimuli, without obstructing of the regular biosynthesis of other homeostatic prostanoids. Therefore, the design of mPGES-1 inhibitors can represent a better choice to take control of PGE2 asso- ciated diseases, compared with conventional non-steroidal anti-inflammatory drugs and cyclooxygenase (COX) inhibitors, which are known for their serious side effects. Although there is an intensive effort for the identification of mPGES-1 inhibitors, none of the unveiled molecules so far have reached the clini- cal market. Therefore, the development of novel mPGES-1 inhibitors with proper drug-like properties is still an unmet medical need. As a continuation of our research for the identification of new chemotypes which might inhibit this enzyme, we now report the design and synthesis of 3-aryloxymethyl-5-[(2-oxo- 2-arylethyl)sulfanyl]-1,2,4-triazoles and their oxime derivatives as inhibitors of human mPGES-1. All syn- thesized compounds were characterized by FTIR, 1H NMR, 13C NMR (for compounds 12, 14, 15, 26, 27), HMBC (for compounds 6, 7, 8, 16, 19, 23, 28), and MS data. Twenty-four target compounds 7–30 were screened for their mPGES-1/COX-2 inhibitory activities as well as their cytotoxicity. Of these compounds, 20 and 24 showed potent mPGES-1 inhibition by IC50 values of 0.224±0.070 μM and 1.08±0.35 μM, re- spectively. These two compounds have also been observed to inhibit angiogenesis in matrigel tube forma- tion assay with no toxicity toward HUVEC cells. In silico studies were also held to understand inhibition mechanisms of the most active compounds using molecular docking, molecular dynamics calculations and ADMET predictions.

A focused in-house library of about 1000 compounds comprising various heterocyclic motifs in combination with structural fragments similar to β-phenylethylamine or tyramine was screened for the agonistic activity towards trace amine-associated receptor 1 (TAAR1). The screening yielded two closely related hits displaying EC50 values in the upper submicromolar range. Extensive analog synthesis and testing for TAAR1 agonism in a BRET-based cellular assay identified compound 62 (LK00764) with EC50 = 4.0 nM. The compound demonstrated notable efficacy in such schizophrenia-related in vivo tests as MK-801-induced hyperactivity and spontaneous activity in rats, locomotor hyperactivity of dopamine transporter knockout (DAT-KO) rats, and stress-induced hyperthermia (i.p. administration). Further preclinical studies are necessary to evaluate efficacy, safety and tolerability of this potent TAAR1 agonist for the potential development of this compound as a new pharmacotherapy option for schizophrenia and other psychiatric disorders.

Akdemir, Atilla/0000-0001-8416-0471 WOS: 000442985800005 In this study, 1-(4-substitued benzyl)-3,5-diphenyl-1H-1,2,4-triazoles (2 a-e) and ethyl(3,5-diphenyl-/H-1,2,4-triazole-1-yl) acetate (3) were synthesized starting from 3,5-diphenyl-/H1,2,4-triazole (1). The ethyl acetate derivative (3) was converted to 2-(3,5-diphenyl-1H-1,2,4-triazole-1-yl)acetohydrazide (4) in ethanolic medium with hydrazine hydrate. The reaction of the acetohydrazide (4) with suitable isothiocyanates generate 2-[(3, 5-diphenyl-1H-1,2,4-triazole-1-yl)acetyl]-4-methyl/phenyh-Ithiosemicarbazide (5a,b). The cyclization of the thiosemicarbazide (5a,b) in the presence of NaOH (2 M) resulted in the formation of 5-[(3,5-diphenyl-1H-1,2,4-triazole-1-yl)methyl]-4methyl/phenyl-2,4-dihidro-3H-1,2,4-triazole-3-thiol (6a,b). Finally, the synthesized 1,2,4-triazole-3-thiols (6a,b) were converted to their 5-substituebenzyl derivatives (7 a-j). All of the synthesized compounds (1-7) were also examined for antioxidant capacities, and antiurease and anti-acetylcholinesterase (anti-AChE) activities. It has been found that antioxidant capacity and anti-urease activity of the compound 7f is very good in biochemically active compounds. Karadeniz Technical University, BAP, TurkeyKaradeniz Teknik University [FBA-2014-89] The authors are thankful for the financial support from Karadeniz Technical University, BAP, Turkey, through Project number FBA-2014-89.

A general method for the synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed from reaction of amidrazones with ethyl azodicarboxylate and triethylamine (Mitsunobu reagent) in EtOH. This highly regioselective one-pot process provides rapid access to highly diverse triazoles. The reaction was explained, based on Mitsunobu reagent oxidizing ethanol to acetaldehyde, which would then react with amidrazones to give the substituted 3-methyltriazoles. A [2 + 3] cycloaddition reaction between two oxidized forms of amidrazones produced the second type of triazoles. X-ray structure analyses proved the structure of each type of product. [GRAPHICS] .

WOS: 000440458100007, In this study K-alpha 1, K-alpha 2 and KLL Auger line widths were determined semi-empirically by using K shell fluorescence yields of sulfur even if K-alpha X-ray lines cannot be resolved in our detector system. The samples of 1,2,4-Triazoles were irradiated by an annular 50 mCi Fe-55 radioactive source. It was found that halogens (e.g. Cl) and electron donating groups (e.g. -CH3, -OCH3, -OH etc.) have a crucial effect onto the valence shell structure of sulfur. The expansion of Auger line widths was attributed to the Coster-Kronig transitions in L shells which are energetically possible. (C) 2018 Elsevier B.V. All rights reserved.

New acyclonucleoside analogs tethered by a 1,2,4-triazole scaffold were synthesized through the condensation of 4-amino-5-(2-phenyleth-1-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (2) with benzaldehyde followed by the alkylation of the resulting Schiff base (3)with 2-bromoethanol, 3-chloropropanol and/or 3-chloropropan-1,2-diol. Voltammetric studies were carried out for the analysis of 1 × 10−6 mol L−1 of the newly synthesized acyclonucleoside analogs (4–6) using square wave-adsorptive stripping voltammetry (SW-AdSV). The sharp voltammetric peak and high reduction current were recorded using a Britton–Robinson B–R pH 10 buffer at Ep = −1250 mV on the hanging mercury drop surface (HMDE) and Ag/AgCl reference electrode. Several experimental conditions were studied, such as the supporting electrolytes, the pH, and the accumulation time, as well as the potential, the scan rate, the frequency and the step potential for 4-benzylideneamino-5-(2-phenyleth-1-yl)-3-[(2,3-dihydroxyprop-1-yl)thio]-1,2,4-triazole (6). The analytical performance of the voltammetric technique was investigated through the analysis of the calibration curve, the detection limit, the recovery and the stability. The voltammetric analytical applications were evaluated by the recovery of compound (6) in the urine and plasma samples. The HPLC technique was also applied for the separation of compound (6) from interference using a C-18 (5 μm) column with UV detection at 254 nm.

The present study describes an efficient and ecofriendly, ultrasound, one-pot click cycloaddition approach for the construction of a novel series of 1,4-disubstituted-1,2,3-triazoles tethered with fluorinated 1,2,4-triazole-benzothiazole molecular conjugates. It involved three-component condensation of the appropriate bromoacetamide benzothiazole, sodium azide and 4-alkyl/aryl-5-(2-fluorophenyl)-3-(prop-2-ynylthio)-1,2,4-triazoles 4a-e through a Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction. This approach involves in situ generation of azidoacetamide benzothiazole, followed by condensation with terminal alkynes in the presence of CuSO4/Na-ascorbate in aqueous DMSO under both conventional and ultrasound conditions. Some of the designed 1,2,3-triazole conjugates 6a-o were recognized for their antimicrobial activity against some bacterial and fungal pathogenic strains.

A new series of 4-benzyl-6,7,8,9-tetrahydro[1]benzothieno[3,2- e ][1,2,4]triazolo[4,3- a ] pyrimidines was synthesized motivated by the widely reported anticancer activity of thieno[2,3- d ]pyrimidines and triazolothienopyrimidines. The in vitro cytotoxic activity of some selected compounds was evaluated against two human cell lines: prostate cancer (PC-3) and colon cancer (HCT-116). A preliminary study of the structure-activity relationship of the target compounds was discussed. Most of the synthesized compounds showed remarkable activity on the tested cell lines, while compound 16c had the highest potency against the PC-3 cell line with an IC 50 of 5.48 μM compared to Doxorubicin (IC 50 =7.7 μM), the reference standard used in this study. On the other hand, 6c and 18c were the most active against HCT-116 (IC 50 =6.12 and 6.56 μM, respectively) relative to IC 50 =15.82 μM of the standard. Thus, some of the synthesized thienopyrimidine derivatives, specially 6c , 16c and 18c , have the potential to be developed into potent anticancer agents.

WOS: 000347145200004 In the present investigation, the key intermediate acetohydrazide derivative 5 was synthesized starting from 3-(4-methoxybenzyl)-4-amino-4,5-dihydro-1,2,4-triazol-5-one (1) by a four-step reaction. Thiosemicarbazides 6a-f and arylidenehydrazide derivatives 8a-d were obtained from compound 5. the cyclization of compounds 6a-f in the presence of NaOH resulted in the formation of compounds 7a-f. the compounds were characterized by IR, H-1 NMR, C-13 NMR spectroscopy, elemental analysis and mass spectial studies. the compounds were tested for their anti-lipase, anti-alpha-glucosidase and anti-mycobacterial activities. Compounds 6b and 8c exhibited excellent anti-lipase activity, and compound 8d showed excellent anti-alpha-glucosidase activity. Compounds 3 and 4 exhibited good anti-tuberculosis activity. Karadeniz Technical University, BAP, TurkeyKaradeniz Technical University [10020] The support provided by Karadeniz Technical University, BAP, Turkey (project no. 10020) is gratefully acknowledged.

In the present investigation, a series of new Schiff bases 4a–f were synthesized by the condensation of N-[(4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl)methyl]-4-substituted-benzamides 3a–b with various substituted aromatic aldehydes in ethanol–dioxane mixture using catalytic amount of sulfuric acid. The starting materials 3a–b were in turn synthesized by the fusion of benzoyl glycine/substituted benzoylglycine with thiocarbohydrazide. Newly synthesized compounds were characterized by IR, NMR, mass spectra and elemental analyses. All the compounds were evaluated for their antibacterial and antifungal activity using the Minimum Inhibition Concentration (MIC) method by serial dilution technique. Few of the compounds were found to be biologically active.

The title compound, C15H12N4O2, contains two independent molecules in the asymmetric unit. These differ in terms of dihedral angles that the phenyl and 2-pyridyl rings subtend with the central five-membered ring; 15.2 (2) and 2.9 (2)°, respectively, in one molecule, 8.9 (2) and 5.1 (2)°for the second. In the crystal, the independent molecules each self-associate to form layers through N—H...O and C—H...O hydrogen bonding. The layers associate through π–π interactions between the phenyl rings and isolated carbon–carbon double bonds [shortest midpoint–centroid distance = 3.347 (4) Å]. The crystal studied was refined as a two-component twin.

1,2,4-Triazole3-thiones are good scaffolds for preparation of new lead compounds. Their derivatives attracted the attention of chemists due to their wide spectrum of biological activities. Alkylsulfanyl-1,2,4-triazoles have three nucleophilic sites (nitrogens) ready for reaction with electrophiles. Herein, new regioselective isomers were synthesized by the reaction of benzylsulfanyl-1,2,4-triazole with various dihaloalkanes. Regioselectivity was determined by X-ray crystallography and NMR. Coupling of 3-benzylsufanyl-5-(1H-indolyl)-1,2,4-triazole with dibromomethane, 1,2-dichloroethane, 1,3-dibromopropane and di(bromomethyl)quinoxaline was investigated in the presence of potassium carbonate in acetone. In the case of dibromomethane three different bis(triazolyl)methane isomers (–N 1–CH2–N 1-4, –N 1–CH2–N 2-5, –N 2–CH2–N 2-6) were formed in which the two bromide atoms were replaced by two triazole moieties. Among these isomers the reaction was regioselective towards the –N 1–CH2–N 2-5 isomer due to the steric effect. In the case of 1,3-dibromopropane two compounds were obtained due to the alkylation at N(2) to give 2-(3-bromopropyl)-triazole 8 and alkylation at N(1) was followed by cyclization at the indole nitrogen to form a condensed indolo-triazolo-diazepine 10. Upon alkylation of 3-benzylsufanyl-5-(1H-indolyl)-1,2,4-triazole with di(bromomethyl)quinoxaline, two bis(triazolyl-methyl)quinoxaline isomers were separated and characterized as (–N 1–CH2–N 1–) 11 and (–N 2–CH2–N 2–) 12. Single-crystal X-ray diffraction assisted the elucidation and confirmation of the structures of the isomers. An AM1 theoretical study explained the regioselectivity of the alkylation. On reacting S-protected 1,2,4-triazoles with various alkylating agents, only N(1) and N(2) attack the electrophilic carbons. N(2) alkylated isomers are preferentially formed.

Производные 1,2,4-триазола получили большое применение в медицинской практике благодаря широкому спектру биологического действия и низкой токсичности, что, в свою очередь, обусловлено присутствием в их структуре триазольного цикла. Именно поэтому данный класс органических гетероциклических соединений является особенно интересным и перспективным для исследования его физико-химических и биологических свойств. С целью поиска новых потенциально биологически активных веществ было синтезировано 13 новых соединений, ранее не описанных в научной литературе, – 3-(4-(трет-бутил)-фенил)-5-(R-илтио)-4H-1,2,4-триазол-4-аминов, а также предложены препаративные методы их синтеза. Структура новых соединений была изучена с помощью современных инструментальных методов анализа (хромато-масс-спектрометрия, ИК, 1Н ЯМР-спектроскопия и элементный анализ). Установлено, что результаты исследований подтверждают структуру данных соединений. Это свидетельствует о возможности их дальнейшего применения в биологических исследованиях., Aim. 1,2,4-triazole derivatives are widely used in medical practice due to its wide range of biological effect and small toxicity. This fact makes this class of organic heterocyclic compounds especially interesting and promising for the study of their physical-chemical and biological properties. Thirteen novel compounds, namely 3-(4- (tert-butyl)phenyl)-5-(R-ylthio)-4H-1,2,4-triazole-4-amines, that were not previously described in the literature, have been synthesized with the aim of search for new potentially biologically active compounds.Methods and results. In order to create new biologically active compounds 13 novel 3-(4-(tert-butyl)phenyl)-5-(R-ylthio)-4H-1,2,4-triazole-4-amines have been synthesized, preparative methods of their synthesis have been proposed, the structure of synthesized compounds has been confirmed by IR-, 1H NMR-spectroscopy, chromatography-mass spectrometry and elemental analysis. In addition, the compounds have been tested for antimicrobial and antioxidative activities.Conclusions. A preparative methods of synthesis of 3-(4-(tert-butyl)phenyl)-5-(R-ylthio)-4H-1,2,4-triazol-4-amines that can be used for chemical modeling of new biologically active compounds are described. The structure of the synthesized compounds was confirmed by complex of modern methods of investigation, namely: IR-, 1H NMR-spectroscopy, chromatography-mass spectrometry and element analysis.This indicates the possibility of using these substances to further biological studies., Похідні 1,2,4-тріазолу отримали широке застосування в медичній практиці завдяки різноманітному спектру біологічної дії та низькій токсичності. Саме тому цей клас органічних сполук є особливо цікавим і перспективним для дослідження його фізико-хімічних, біологічних властивостей. З метою пошуку нових потенційно біологічно активних речовин синтезували 13 нових сполук, котрі не були описані раніше в науковій літературі, – 3-(4-(трет-бутил)феніл)-5-(R-ілтіо)-4H-1,2,4-тріазол-4-амінів, а також запропонували препаративні методи їхнього синтезу. Структуру нових речовин вивчили за допомогою сучасних інструментальних методів аналізу (хромато-мас-спектрометрія, ІЧ-, 1Н ЯМР-спектроскопія та елементний аналіз). Встановили: результати роботи підтверджують структуру цих сполук, що свідчить про можливість надалі їх застосовувати в біологічних дослідженнях.

New 5-(2-thienyl)-1,2,4-triazoles and 5-(2-thienyl)-1,3,4-oxadiazoles namely, N-[3-mercapto-5-(2-thienyl)-1,2,4-triazol-4-yl]-N'-arylthioureas 4a–e, 2-arylamino-5-(2-thienyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles 5a–e, 3-arylaminomethyl-5-(2-thienyl)-1,3,4-oxadiazoline-2-thiones 7a–e, 3-(N-substituted anilinomethyl)-5-(2-thienyl)-1,3,4-oxadiazoline-2-thiones 8a, b and 3-(4-substituted-1-piperazinylmethyl)-5-(2-thienyl)-1,3,4-oxadiazoline-2-thiones 9a–f, were prepared. The synthesized compounds were tested for in vitro activities against certain strains of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compound 9a displayed marked broad spectrum antibacterial activity, while compounds 4d, 5e, 7b, 7c, 7d, 9b, 9c and 9d were highly active against the tested Gram-positive bacteria. None of the synthesized compounds were proved to be significantly active against Candida albicans.

WOS: 000251996400018 Some new N-alkoxycarbonyl-N ''-benzoyl-benzamidrazones (p-toluamidrazones) 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, H-1 NMR, C-13 NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer (MCF7), non small cell lung cancer (NCI-H460), and CNS cancer (SF-268) at the National Cancer Institute (NCI), USA, which were found to exhibit low antiproliferative activity.

Здійснили дослідження протимікробної та протигрибкової активності серед S-похідних 7-((3-тіо-4-R-4Н-1,2,4-тріазол-3-іл)метил)теофіліну. Як набір стандартних тест-штамів взято Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomоnas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Встановили, що найбільш активними серед сполук, що одержали, є алкілпохідні 7-((3-тіо-4-R-4Н-1,2,4-тріазол-3-іл)метил)теофіліну. Серед синтезованих солей привернув увагу амоній 2-(5-((теофілін-7-іл)метил)-4-феніл-4Н-1,2,4-тріазол-3-ілтіо)ацетат, який виявився активним стосовно Staphylococcus aureus. Визначили перспективний клас сполук для наступних досліджень за цим видом біологічної активності., Aim. The research of antimicrobial and antifungal activity of 7-((3-thio-4-R-4H-1,2,4-triazoles-3-yl)methyl)theophylline S-derivatives has been erformed.Methods and results. Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomоnas aeruginosa ATCC 27853, Candida albicans ATCC 885-653 have been taken as a set of standard test-strains. It has been proved that the most active alkyl-derivatives are 7-((3-thio-4-R-4H-1,2,4-triazole-3-yl)methyl)theophylline. Among the synthesized salts, which turned to be active against Staphylococcus aureus, the 2-(5-((theophylline-7-yl)methyl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetate ammonium has attracted our attention.Conclusion. The perspective class of compounds for further research on this type of biological activity has been defined., Проведены исследования противомикробной и противогрибковой активности среди S-производных 7-((3-тио-4-R-4Н-1,2,4-триазол-3-ил)метил)теофиллина. В качестве набора стандартных тест-штаммов взято Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomоnas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Установлено, что наиболее активными среди полученных соединений являются алкилпроизводные 7-((3-тио-4-R-4Н-1,2,4-триазол-3-ил)метил)теофиллина. Среди синтезированных солей наибольшее внимание привлек аммоний 2-(5-((теофиллин-7-ил)метил)-4-фенил-4Н-1,2,4-триазол-3-илтио)ацетат, который оказался активным по отношению к Staphylococcus aureus. Определён перспективный класс соединений для дальнейших исследований по данному виду биологической активности.

В создании оригинального препарата основную роль играет подбор, синтез и установление биологических свойств нового соединения. C целью поиска новых биологически активных соединений были синтезированы 3-(алкилтио)-4-R-5-(тиофен-2-илметил)-4H-1,2,4-триазолы, где R – метил, этил, фенил, реакцией алкилирования 4-R-5-(тиофен-2-илметил)-4H-1,2,4-триазол-3-тиолов галогеналканами (1-бромбутаном, 1-бромпентаном, 1-бромгексаном, 1-бромгептаном, 1-бромоктаном, 1-бромнонаном, 1-бромдеканом) в среде н-бутанола и изучены их физико-химические свойства современными физико-химическими методами анализа: элементного анализа, ИК-спектроскопии, а их индивидуальность – методом ВЭЖХ-МС. Это свидетельствует о возможности дальнейшего изучения биологического действия синтезированных соединений., Aim. Selection, synthesis and biological properties of new compound play major role in creating original medicines.Methods and results. Therefore, to find new bioactive compounds 3-(alkylthio)-4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazoles, where R - methyl, ethyl, phenyl, have been synthesized, by alkylation reaction of 4-R-5-(thiophene-2-ylmethyl)-4H-1,2,4-triazole-3-thiols with 1-bromobutane, or 1-bromopentane, or 1-bromohexane, 1-bromoheptane, 1-bromooctane, 1-bromononane, 1-bromodekane in the n-butanol medium and their physical-chemical properties have been studied using modern physical-chemical methods of analysis, elemental analysis, IR spectroscopy, and their individuality using HPLC-MS.Conclusion. This suggests the possibility of further studying the biological effect of the synthesized compounds., У створенні оригінального препарату основну роль відіграє підбір, синтез і встановлення біологічних властивостей нової сполуки. З метою пошуку нових біологічно активних сполук було синтезовано 3-(алкілтіо)-4-R-5-(тіофен-2-ілметил)-4H-1,2,4-тріазоли, де R – метил, етил, феніл, реакцією алкілування 4-R-5-(тіофен-2-ілметил)-4H-1,2,4-тріазол-3-тіолів галогеналканами (1-бромбутаном, 1-бромпентаном, 1-бромгексаном, 1-бромгептаном, 1-бромоктаном, 1-бромнонаном, 1-бромдеканом) у середовищі н-бутанолу та вивчено їхні фізико-хімічні властивості сучасними фізико-хімічними методами аналізу: елементного аналізу, ІЧ-спектроскопії, а їх індивідуальність – методом ВЕРХ-МС. Це свідчить про можливість надалі вивчати біологічну дію синтезованих сполук.

В современной медицинской практике используют большое количество лекарственных средств. За последние десятилетия лекарственные препараты на основе 1,2,4-триазола заняли основательное место в медицине и фармации всего мира благодаря противораковым, антидепрессивным, кардиопротекторным и антиоксидантным свойствам. Кроме высоких результатов фармакологического действия производные триазола характеризуются низкими показателями острой и хронической токсичности, обусловливая актуальность дальнейших исследований. С целью обобщения информации об участии 1,2,4-триазола в химических превращениях с помощью библиосемантического метода изучили специализированную литературу за последние 10 лет. Установлено, что наличие амино- и тиольной группы придает высокую реакционную способность исходным соединениям. Это свидетельствует о возможности расширения спектра биологического действия и рекомендации самого активного соединения для углубленных фармакологических исследований., Aim. A number of references of the last ten years have been carefully studied with bibliosemantic method to compile information on the participation of 1,2,4-triazoles in chemical reactions.Introduction of new domestic drugs intopractice, which could compete with expensive imported drugs,is oneof the most important social and economic problem sof the pharmaceutical industry. The key step in the creation of original drugs is a purposeful synthesis of biologically active substances with pronounced pharmacological effect and low toxicity.Results. It has been established that the presence of amino and thiol groups provides high reactivity of the starting compounds.It is known that 1,2,4-triazole nucleus is a structural fragment of many synthetic drugs with antifungal (fluconazole, intrakonazol), antidepressant (trazodone, alprazolam), antiviral (thiotriazolin), wound healing and hepatoprotective activity. That’s why the 4-amino and 3-thio-1,2,4-triazoles have attracted our attention as potential biologically active compounds which can become the basis of future drugs. Quite powerful material has been gained in the last decade in terms of chemical reactions with the participation of 4-amino and 3-thio-1,2,4-triazoles. This is due to the fact that 1,2,4-triazoles are used not only to create drugs, but also for the manufacture of various products, which are widely used in agriculture, industry, etc.But there are no well-known information in recent years that could generalize chemical conversion with the participation of amino- and thio- derivatives of 1,2,4-triazoles.That is why this purpose became the main goal of our work. Condensation reaction with aromatic aldehydes in a series of 4-amino-3-thio-1,2,4-triazoles has been studied.The article presents data on the analysis further change with above named substances, their participation in cyclization reactions, condensation of aromatic aldehydes, interaction with halogen carbonyl compounds with aryl nitriles of carboxylic acids and conversation 1,2,4-triazole-3-thioacetic acids in sulfoaceticacids and ester receiving, salts and hydrazides to broaden the search range of pharmacologically active substances.The structure of the synthesized compounds as example 5-(4-dimethylaminobenzylidene)-2-methylthiazol(3,2-b)-1,2,4-triazole-6-one has been confirmed with X-ray examination. Conclusion. It indicates the possibility of expanding spectrum of biological actions and further recommendations of most active compound for enhanced pharmacological studies., У сучасній медичній практиці використовують чималу кількість лікарських засобів. За останні десятиліття лікарські препарати на основі 1,2,4-тріазолу посіли чільне місце в медицині та фармації всього світу завдяки протираковим, антидепресивним, кардіопротекторним та антиоксидантним властивостям. Крім високих результатів фармакологічної дії похідні тріазолів мають низькі показники гострої та хронічної токсичності, що надає актуальності наступним дослідженням. З метою узагальнення інформації щодо участі 1,2,4-тріазолів у хімічних перетвореннях за допомогою бібліосемантичного методу вивчили фахову літературу за останні 10 років. Встановили, що наявність аміно- та тіольної групи надає високу реакційну здатність вихідним сполукам. Це свідчить про можливість розширення спектра біологічної дії та рекомендації найактивнішої сполуки для поглиблених фармакологічних досліджень.

В рамках данной работы осуществлен синтез большой серии амидразонов, аминогруппа которых является частью циклического фрагмента, и проведено исследование реакций с этилхлорформиатом, хлорангидридом циклогексанкарбоновой кислоты и оксалилхлоридом. Получены бис(амидразоны) с циклическими, ароматическими и линейными мостиковыми фрагментами. Изучены реакция бис(амидразонов) с ацетоном. В результате были получены новые пиперазин-1-карбоксилаты, диацилгидразонопиперазин и гексаазоциклододецин. Проведено комплексное исследование структуры полученных соединений с помощью экспериментаьных (масс-спектры, ИК-спектры, спектры ЯМР 1Н и 13С, рентгеноструктурный анализ) и теоретических методов. Amidrazones with cyclic amino group were obtained by reaction of hydrazonoyl chloride with diamines. Interaction of synthesized amidrazones with oxalyl dichloride, ethylchloroformate and cyclohexanecarboxylic chloride were investigated and as a result, it was prepared several new heterocyclic products: hexaazacyclododecine, piperazine-1-carboxylates and diacylhydrazonopiperazines. Also were obtained new bis(amidrazones) with various bridging moieties. Investigation of the reaction of bis(amidrazones) with acetone was carried out. A detailed of the structure of the synthesized compounds were made by spectral methods including mass, IR, 1H and 13C NMR, RSA data, and by theoretical investigation with the quantum chemistry calculation. Программа развития УрФУ на 2013 год (п.1.2.2.3)

Introduction: 1,2,4-triazoles and its derivatives have been reported to possess anti-inflammatory, analgesic, antimicrobial, anticancer, antitumor, antitubercular, anticonvulsant, openers of Ca-activated potassium (Maxi-K) channels, antiviral properties, hypoglycemic, anxiolytic and antidepressant activity. Therefore, 1,2,4-triazole seems to be an important pharmacophore. Materials and Methods: The synthesis of 4-(substituted ethanoyl) amino-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) were prepared following six step starting 4-methoxy benzoic acid and using different secondary amines and were characterized with the help of FT-IR, 1 H, 13 C NMR, FAB Mass and nitrogen analysis. These synthesized compounds (6a-o) were then evaluated for anti-inflammatory activity by carrageenan induced paw edema method.Out of these synthesized compounds, some (6f, i and k) were evaluated for antinociceptive activity by Hot plate method and Tail immersion method. Results and Discussion: The synthesis of 4-(substituted amino)-3-mercapto-5-(4-methoxy) phenyl-1,2,4-triazoles (6a-o) was accomplished. The IR spectra exhibited characteristic bands for C-N, C=N, SH and C=O at 1350-1360, 1511-1548, 2520-2594.3 and 1650-1719 cm -1 . The C-O-C asymmetric and symmetric str. was at 1250-1254 and 1027-1079.3 cm -1 respectively. In 1 H-NMR spectra, a singlet of CONH was found in the range of δ 9.92-10.18 ppm and another singlet of thiol group was observed in the range of δ 8.63-9.92 ppm. A singlet of Ar-OCH 3 was also found between δ 3.57-3.91 ppm. In 13 C- NMR spectra, C-3 and C-5 of the 1,2,4 - triazole nucleus were observed in the range of δ 147-166.9 ppm. Carbonyl carbon and methylene carbon of -NHCOCH 2 N< were found between δ 166.5-177.5 and δ 47.1-62 ppm respectively. Acute toxicity study was donr following OECD-423 and cut-off dose was found to be between 1000-1500 mg/kg body weight. At the dose level of 100 mg/kg, 6f, 6i and 6k exhibited appreciable inhibition of oedema especially 6k exhibiting a percentage of oedema inhibition of 40.28%, which was comparable to that of the standard drug indomethacin (62.50% at 10mg/kg dose). Among the compounds tested, compound 6k exhibited good anti-nociceptive activity in both methods used. Pethidine (20mg/kg body weight s.c) is used as the standard drug. Conclusion: SAR of these synthesized compounds shows that substitution with heterocyclic moiety at C-2 of the acetamido group at position 4 of the 1,2,4-triazole produces appreciable activity as compared to substitution with aliphatic moieties since among all the synthesized compounds, the most active ones are 6f, 6i and 6k that have piperdine, 1-benzyl piperazine and morpholine group, respectively at C-2 of the acetamido group at position 4 of the 1,2,4-triazole.

In the present study we describe the synthesis of a new series of 1,2,4-triazoles: [3-(arylmethyl)thio-5-aryl-4H-[1,2,4]triazol-4-yl]acetic acids 5a-g, [5-(arylmethyl)thio-3-aryl-1H-[1,2,4]triazol-1-yl]acetic acids 8a-d, and [3-(aryl-methyl)thio-5-aryl-1H-[1,2,4]triazol-1-yl] acetic acids 9a-d. These compounds were tested in binding assays to evaluate their ability as ligands for human ET(A) and ET(B) receptors stably expressed in CHO cells; some of the tested compounds showed affinity in the micromolar range.

The reaction of some fluorinated 1,2,4-oxadiazoles in the presence of methylamine or propylamine has been investigated. The irradiation in methanol or acetonitrile leads with acceptable yields to the corresponding fluorinated 1- methyl- or 1-propyl-1,2,4-triazole.

Ebtehal S Al-Abdullah,1 Hanadi H Asiri,1 Siham Lahsasni,2 Elsayed E Habib,3 Tarek M Ibrahim,4 Ali A El-Emam1 1Department of Pharmaceutical Chemistry, College of Pharmacy, 2Department of Chemistry, College of Sciences, King Saud University, Riyadh, 3Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Medinah, Saudi Arabia; 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt Abstract: The reaction of 5-(1-adamantyl)-4-phenyl-1,2,4-triazoline-3-thione (compound 5) with formaldehyde and 1-substituted piperazines yielded the corresponding N-Mannich bases 6a–f. The reaction of 5-(1-adamantyl)-4-methyl-1,2,4-triazoline-3-thione 8 with various 2-aminoethyl chloride yielded separable mixtures of the S-(2-aminoethyl) 9a–d and the N-(2-aminoethyl) 10a–d derivatives. The reaction of compound 5 with 1-bromo-2-methoxyethane, various aryl methyl halides, and ethyl bromoacetate solely yielded the S-substituted products 11, 12a–d, and 13. The new compounds were tested for activity against a panel of Gram-positive and Gram-negative bacteria and the pathogenic fungus Candida albicans. Compounds 6b, 6c, 6d, 6e, 6f, 10b, 10c, 10d, 12c, 12d, 12e, 13, and 14 displayed potent antibacterial activity. Meanwhile, compounds 13 and 14 produced good dose-dependent anti-inflammatory activity against carrageenan-induced paw edema in rats. Keywords: adamantane derivatives, 1,2,4-triazoles, N-Mannich bases, antimicrobial activity, anti-inflammatory activity

Вивчення фізико-хімічних характеристик, а також встановлення закономірностей мас-спектрометричного розпаду є актуальними завданнями сучасної фармацевтичної науки, мають як науковий інтерес, так і практичну значущість. Мета експерименту – підтвердження індивідуальності та дослідження мас-спектрометричного розпаду для молекули натрій 2-(4-метил-5-(тіофен-2-іл)-4Н-1,2,4-тріазол-3-ілтіо)ацетату. Дослідження виконали на приладі LC MS/MS: LTQ Orbitrap. Після виконання МС сканування встановили, що максимальний пік на хроматограмі відповідає іону з m/z 256,0208, а емпірична формула досліджуваної сполуки – C9H9N3O2S2. MS/MS аналіз 2-(4-метил-5-(тіофен-2-іл)-4Н-1,2,4-тріазол-3-ілтіо)ацетатної кислоти (MH+ з m/z 256,0208) показав, що під дією напруги при зіткненні з молекулами гелію в комірці зіткнень відбувається розпад молекули на деякі фрагменти. Встановили, що руйнування молекули спочатку здійснюється з відривом молекули води від карбоксильної групи. Під впливом зіткнення з газом наступною може відриватися карбоксильна група. При наступному розпаді руйнується зв’язок між атомом сульфуру та оцтовим залишком або ж відбувається розрив ковалентного зв’язку між сульфуром і вуглецем 1,2,4-тріазолу., The study of physical and chemical characteristics and establishing patterns of mass spectrometric fragmentation are the actual tasks of modern pharmaceutical science, have both scientific interest and practical importance.Aim. The purpose of our experiment was to confirm the identity and study patterns of mass spectrometric decomposition for sodium 2-(4-methyl-5-(thiophene-2-yl) -4H-1,2,4-triazoles-3-ilthio) acetate.Methods and results. The study was carried out on the apparatus LC MS / MS: LTQ Orbitrap. After completing MS scan, it has been established that the maximum peak in the chromatogram corresponds protonated ion 2-(4-methyl-5-(thiophene-2-yl)-4H-1,2,4-triazoles-3-ylthio)acetic acid m/z 256.0208, and empirical formula test compound - C9H9N3O2S2. MS/MS MH+ analysis showed that protonated molecule of the 2-(4-methyl-5-(thiophene-2-yl)-4H-1,2,4-3-triazole-3-ylthio)acetic acid under voltage in contact with molecules of helium in the collision cell was disintegrated from m/z 256.0208 into some fragments. The first time the mass spectrometric investigation sodium 2-(4-methyl-5-(thiophene-2-yl)-4H-1,2,4-triazoles-3-ylthio) acetate has been undertaken.Conclusions. It has been established that the fragmentation of the molecule initially occurs with the dissociation of water molecule from carboxyl group. Under the influence of gas the next to come off may be a carboxyl group. In course of further dissociation the bond between the sulfur atom and acetic residue is destroyed or disruption of a covalent bond between sulfur and carbon of 1,2,4-triazole occurs., Изучение физико-химических характеристик, а также установление закономерностей масс-спектрометрического распада являются актуальными задачами современной фармацевтической науки, имеют как научный интерес, так и практическую значимость. Целью нашего эксперимента было подтверждение индивидуальности и исследование масс-спектрометрического распада для молекулы натрий 2-(4-метил-5-(тиофен-2-ил)-4Н-1,2,4-триазол-3-илтио)ацетата. Исследование проведено на приборе LC MS/MS: LTQ Orbitrap. После выполнения МС сканирования установлено, что максимальный пик на хроматограмме соответствует иону с m/z 256,0208, а эмпирическая формула исследуемого соединения – C9H9N3O2S2. MS/MS анализ 2-(4-метил-5-(тиофен-2-ил)-4Н-1,2,4-триазол-3-илтио)ацетатной кислоты (MH+ з m/z 256,0208) показал, что под действием напряжения при столкновении с молекулами гелия в ячейке столкновений проходит распад молекулы на некоторые фрагменты. Установлено, что разрушение молекулы сначала проходит с отрывом молекулы воды от карбоксильной группы. Под влиянием столкновения с газом следующей может отрываться карбоксильная группа. При дальнейшем распаде разрушается связь между атомом серы и уксусным остатком или же происходит разрыв ковалентной связи между серой и углеродом 1,2,4-триазола.

Fused triazoles derivatives have been prepared from the reaction of the starting material 4 with some electrophilicreagents. The structures of all new compounds have beenestablished on the basis of elemental analysis and spectroscopicdata. All the synthesized compounds have been screened for their antibacterial activity. 1,2,4-Triazole derivatives 4, 14 and 15 exhibited a good antibacterial activity compared with the standard antibiotic Gentamycin. The tautomeric equilibria of the compounds 4 and 15 thione and thiol form were studied by quantum chemical calculations semi-empirical (AM1, MNDO and PM3) and ab initio level (RHF/3-21G* and RHF/6-31G*) in the gas phase.