3,6-二取代苯基-二-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑衍生物的合成

以2,5-二巯基-1,3,4-噻二唑为原料, 与水合肼缩合, 生成2,5-二肼基-1,3,4-噻二唑. 2,5-二肼基-1,3,4-噻二唑与苯甲酰氯反应生成2,5-二酰肼基-1,3,4-噻二唑, 以POCl₃为环合剂环合酰肼基-1,3,4-噻二唑, 合成3,6-二取代苯基- 二-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑衍生物, 合成的新化合物的结构通过元素分析、红外光谱、核磁共振氢谱和质谱予以证实, 并提出了环化反应机理.     

Tetragonal-pyramidal complex of copper nitrate with 2-Amino-5-ethyl-1,3,4-thiadiazole

A complex compound of Cu(II) nitrate with 2-amino-5-ethyl-1,3,4-thiadiazole was synthesized and its structure was studied by the methods of IR spectroscopy and X-ray crystal analysis. The complex has the composition Cu(NO₃)₂(2-amino-5-ethyl-1,3,4-thiadiazole)₄ with four molecules of the heterocyclic ligand (coordination through nitrogen atoms of thiadiazole rings) and one of nitrate ions (the other is replaced in the second sphere) entering into the coordination sphere of the complex polyhedron. The internal coordination sphere of the complex has the form of a tetragonal pyramid with 2-amino-5-ethyl-1,3,4-thiadiazole ligands in the sites of its base and the oxygen atom of the nitrate ion in a slightly distorted vertex of the pyramid.     

Synthesis and cytotoxic evaluation of new colchicine derivatives bearing 1, 3, 4-thiadiazole moieties

In search of novel anticancer agents, a series of N-methyl colchiceinamide derivatives (7a-7i) containing 1,3,4-thiadiazole moieties were synthesized, and their structures were confirmed by spectral analysis. Cytotoxicity of these compounds was evaluated by MTT assay in vitro against four human tumor cell lines, i.e. A2780, A549, BEL7402, and MCF-7. The results indicated that most of the derivatives showed significant anticancer activities, particularly, compounds 7h and 7i showed more potent cytotoxic activities of all screened cancer cells than colchicine.     

Structure determination of 2-amino-5-benzylmercapto-1,3,4-thiadiazole and characterization of its copper complex

The crystal structure of 2-amino-5-benzylmercapto-1,3,4-thiadiazole (Ben-SNTD) has been determined. The thiadiazole ring is planar and aromatic, and the 1,3,4-thiadiazole-2-amino-5-thiol moiety is covalently bound to the benzyl group through the sulphur atom. Spectroscopic evaluation and thermal analysis of the complex formed between Ben-SNTD and CuCl₂ indicate a compound with a CuL₂ type structure.     

New Synthetic Routes to 1,3,4-Thiadiazole Derivatives

Different new 1,3,4-thiadiazolopyridine derivatives (6, 8, 20, 28, and 42) were synthesized from 5-cyanomethyl-1,3-4-thiadiazole (1) and activated nitriles. Also, spiro indolono-thiadiazolopyridine (12) was obtained from the reaction of (1) with 2-(2-oxoindolin-3-ylidene)malononitrile (10). Other heterocyclic derivatives at position-5 in the thiadiazole ring were obtained for possible use as antimicrobial agents.     

2,5-二取代-1,3,4-噻二唑衍生物的合成与表征

苯并噁唑啉酮和1,3,4-噻二唑衍生物具有多种生物活性,制备含有苯并噁唑啉酮结构的1,3,4-噻二唑衍生物非常有意义。本文以邻氨基苯酚和尿素为初始原料,经多步合成反应,制备了10个新的2-(芳甲酰氨基)-5-(2-苯并噁唑啉酮-3-甲基)-1,3,4-噻二唑化合物(7a～7j),并利用IR、1H NMR和元素分析对其结构进行了表征。     

New 1,3,4-Thiadiazole Derivatives with Anticancer Activity

We designed and synthesized the 1,3,4-thiadiazole derivatives differing in the structure of the substituents in C2 and C5 positions. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and normal cell line (fibroblasts). The results showed that in both breast cancer cell lines, the strongest anti-proliferative activity was exerted by 2-(2-trifluorometylophenylamino)-5-(3-methoxyphenyl)-1,3,4-thiadiazole. The IC₅₀ values of this compound against MCF-7 and MDA-MB-231 breast cancer cells were 49.6 µM and 53.4 µM, respectively. Importantly, all new compounds had weaker cytotoxic activity on normal cell line than on breast cancer cell lines. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds. The most likely mechanism of action for the new compounds is connected with the activities of Caspase 3 and Caspase 8 and activation of BAX proteins.     

FT-Raman spectroscopy of the reaction of polybutadiene with mercapto-thiadiazoles

Mercapto-thiadiazoles having potential anti-wear behaviour are reacted with polymers with existing viscosity index-improving properties in order to produce materials which may find a use as multifunctional lubricant additives. 2,5-Dimercapto-1,3,4-thiadiazole, 2-amino-5-mercapto-1,3,4-thiadiazole and 2-methyl-5-mercapto-1,3,4-thiadiadiazole were reacted with low MW polybutadiene containing vinyl-1,2, cis-1,4 and trans-1,4 (C=C) groups. The reactions were monitored using FT-Raman spectroscopy in order to determine quantitatively the consumption of the individual structural units when reacted with thiadiazoles. 2,5-Dimercapto-1,3,4-thiadiazole reacted readily with the polybutadiene, achieving 80% reaction within a few hours. The thiadiazole reacted selectively with the order of addition being cis>vinyl>trans. 2-Amino-5-mercapto-1,3,4-thiadiazole and 2-methyl-5-mercapto-1,3,4-thiadiazole were found to react more slowly and hence to a lesser extent (40 and 25%, respectively) over a similar time scale.     

Synthesis,structural characterization,biological activity,and theoretical studies of some novel thioether-bridged 2,6-disubstituted imidazothiadiazole analogues

In this study, thioether-bridged imidazo[2,1-b][1,3,4]thiadiazole derivatives that contained both imidazole and 1,3,4-thiadiazole (compounds 7a-7i and 8a-8i ) were synthesized from the reactions of 2-amino-1,3,4-thiadiazole with phenacyl bromide ( 6a - 6i ) (at yields of 59% to 74%). The structure of the synthesized compounds was characterized using ¹H NMR, ¹³C NMR, Fourier-transform infrared spectroscopy, elemental analysis, mass spectroscopy, and X-ray diffraction analysis. Mycelial growth, mycelial growth inhibition, minimum inhibitory concentration, minimum fungicidal concentration, and lethal dose values against various plant pathogenic fungi were determined for all of the target compounds synthesized in the study. The test results showed that most of the compounds had moderate to good antifungal activity. In addition, the absorption, distribution, metabolism, excretion (ADME) parameters of the compounds were calculated, and it was observed that all of the compounds met the drug-likeness rules in general. Finally, using docking simulations, it was found that compounds 7h , 7i , 8h , and 8i showed high affinity to PDB ID:5TZ1, which is an CYP51 antifungal target structure.     

Synthesis,Reactions, and Anticancer Activity of Some 1,3,4-Thiadiazole/Thiadiazine Derivatives of Carbazole

A novel method for the synthesis of 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives bearing a carbazole moiety is described. Carbazole was transformed into carbazole-9-thiocarbohydrazide in two steps. This compound was allowed to react with various electrophiles to yield 1,3,4-thiadiazole derivatives. The reaction with bifunctional electrophiles led to 1,3,4-thiadiazines. 2-(Carbazol-9-yl)-5,6-dihydro-4H-1,3,4-thiadiazin-5-one reacted with piperidine and formaldehyde to yield the 4-(piperidin-1-ylmethyl) derivative. The reaction with aromatic aldehydes led to the corresponding 6-arylidene derivatives, which were transformed into pyrimidino[4,5-e]-1,3,4-thiadiazines and pyrazolo[3,4-e]-1,3,4-thiadiazines by a reaction with guanidine, acetamidine, or phenylhydrazine, respectively. Structures of the products were confirmed by ¹H NMR, ¹³C NMR, IR, and mass spectrometric measurements. Selected examples of products were screened for anticancer activity.     

Synthesis and pharmacological evaluation of 3-diphenylmethyl-6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles: A condensed bridgehead nitrogen heterocyclic system

A series of 3-diphenylmethyl-6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives (4a–j and 5a–d) were synthesized by condensation of 4-amino-5-diphenylmethyl-4H-1,2,4-triazole-3-thiol with various substituted aromatic acids and aryl/alkyl-isothiocyanates. The structures of synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectroscopic studies. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic, lipid peroxidation and hepatotoxic effects. Compounds 6-(4-chlorophenyl)-3-diphenylmethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (4a) and 6-(2,4-dichlorophenyl)-3-diphenylmethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole(4c) emerged as the most active compounds of the series and were moderately more potent than the standard drug ibuprofen.     

Studies on reactive intermediates. Part I. An approach to the synthesis of 2-phenyl-7-carbethoxy-5H-1,3,4-thiadiazolo[2,3-a]pyrimidin-5-one

2-Phenyltetrazolo[4,5-a]-1,3,4-thiadiazole ( 4 ), in its azido form, reacted with diethyl fumarate and diethyl maleate to give 2-phenyl-7-carbethoxy-5H-1,3,4-thiadiazolo[2,3-a]pyrimidin-5-one ( 5 ). To assign the structure of compound 5 , 2-phenyl-5-carbethoxy-7H-1,3,4-thiadiazolo[2,3-a]pyrimidin-7-one ( 6 ) was prepared from the reaction of 2-amino-5-phenyl-1,3,4-thiadiazole ( 7 ) with diethylacetylene dicarboxylate. Physical properties and spectral data of compound 6 were different from compound 5 . Theoretical and experimental aspects are discussed.     

Synthesis and Antimicrobial Properties of New Thiosemicarbazide, 1,2,4-Triazole,and 1,3,4-Thiadiazole Derivatives of Sulfanylacetic Acid

Abstract

1,2,4-triazole and 1,3,4-thiadiazole derivatives are still considered a viable lead structure for the synthesis of more efficient antimicrobial agents having a broad spectrum of activity. This study presents the synthesis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole and 1,3,4-thiadiazole derivatives. Reaction of 4-phenyl-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thione with ethyl bromoacetate yields the corresponding ethyl acetate (1). In the subsequent reaction with 100% hydrazine hydrate, the hydrazide (2) was obtained, which was converted with isothiocyanates to new acyl derivatives of thiosemicarbazide (3a–l). The cyclization of these compounds in alkaline media resulted in the formation of new derivatives of 1,2,4-triazole (4a–i), whereas in acidic media new derivatives of 1,3,4-thiadiazole (5a,b,g) were obtained. All synthesized compounds were screened for their in vitro antimicrobial activities.     

Synthesis of 3,6-bisubstituted phenyl-bi-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives

2,5-Bihydrazino-1,3,4-thiadiazole (2) was synthesized by condensation of 2,5-bimercapto-1,3,4-thiadiazole (1) with hydrazine hydrate, and compound 2 reacted with acyl chloride to give 2,5-biacylhydrazino-1,3,4-thiadiazole derivatives (3a–3e). Ring closure of compounds 3a–3e was achieved with POCl3 as the cyclization agent giving 3,6-bisubstituted phenyl-bi-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives (4a–4e), respectively. The novel compounds were identified by elemental analysis, and by infrared (IR), 1H-nuclear magnetic resonance (NMR), and mass (MS) spectrometry. The mechanism of the cyclization is also discussed. __________ Translated from Organic Chemistry, 2006, 26(12): 1720–1722 [译自: 有机化学]     

Design,synthesis, and characterization of some new benzimidazole derivatives and biological evaluation

A new series of benzimidazole derivatives ( 1-15 ) containing 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole, and thiazolidinon rings have been synthesized. All new synthesized benzimidazole compounds were confirmed by ¹H NMR, ¹³C NMR spectra, and LC-MS, and they were examined for their antioxidant and antimicrobial activities. Compounds 7 and 1 showed the highest and the lowest antioxidant activities, respectively. The lowest minimum inhibition concentration value found in compound 5 against Enterobacter aerogenes.     

Synthesis and comparative study of the heterocyclic rings on liquid crystalline properties of 2,5-aryl-1,3,4-oxa(thia)diazole derivatives containing furan and thiophene units

A series of heterocyclic liquid crystalline compounds containing 1,3,4-oxadiazole/thiadiazole, furan and thiophene units were synthesised and characterised by means of electrospray ionisation-mass spectrometry (ESI-MS), high-resolution mass spectroscopy (HRMS), ¹H nuclear magnetic resonance (NMR) and ¹³C NMR. The thermal behaviours were investigated by differential scanning calorimetry (DSC) and polarised optical microscopy (POM). The effect of the 1,3,4-oxadiazole, 1,3,4-thiadiazole, furan, thiophene and benzene rings on the liquid crystalline properties was discussed briefly in context with the geometrical and electronic factors. The results showed that the tendency to form mesophases follows the sequence: 1,4-disustituted benzene >2,5-disubstituted thiophene >2,5-disustituted furan and 1,3,4-thiadiazole >1,3,4-oxadiazole.     

Cyclic condensations of 2-amino-1,3,4-thiadiazole with 1,3-dicarbonyl compounds

The reactions of 2-amino-1,3,4-thiadiazole with 1,3-dicarbonyl compounds are described. 2,4-Pentanedione gave 2-thiocyanato-4,6-dimethylpyrimidine while diethylmalonate and ethyl acetoacetate yielded 5-hydroxy-7H-1,3,4-thiadiazolo[3,2-a]pyrimidin-7-one and 7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one, respectively. The structure of the latter compound was confirmed by a synthesis of the alternative isomeric structure (5-methyl-7H-1,3,4-thiadiazolo[3,2-a]pyrirnidin-7-one) from 2-amino-1,3,4-thiadiazole and α-bromocrotonic acid.     

2-氨基-5-烷基-1,3,4-噻二唑修饰环糊精的制备与表征

在N2气保护下, 用单-(6-对甲苯磺酰基)-CD(β-CD-6-OTs)和过量的2-氨基-5-烷基-1,3,4-噻二唑在80 ℃反应2 d, 合成了5种新的2-氨基-5-烷基-1,3,4-噻二唑修饰β-环糊精. 化合物的结构用IR, 1H NMR, 13C NMR, UV, MS和元素分析等方法进行了表征. 由于环糊精的屏蔽效应, 在2-氨基-1,3,4-噻二唑修饰β-环糊精的 1H NMR中, 修饰产物中的噻二唑质子发生了高场位移. 其它的谱图数据同理论值相吻合, 这证明合成与分离方法是可行的. 研究了产物的生物活性, 结果显示部分化合物(2d, 2e)的抗菌活性明显增强.     

Synthesis and Characterization of Some New Heteroaromatic Compounds Having Chirality Adjacent to a 1,3,4‐Thiadiazole Moiety and Their Antimicrobial Activities

Through a cyclization reaction of 2‐phenylbutyric acid with N‐ phenylthiosemicarbazide and POCl₃, novel 1,3,4‐thiadiazole derivatives were synthesized. Their structures were confirmed using IR, ¹H NMR, and ¹³C NMR spectroscopies and elemental analysis. The antibacterial activities of the obtained 1,3,4‐thiadiazole derivatives were tested against Gram‐negative bacteria (Salmonella enteritidis , Salmonella typhimurium , Enterobacter aerogenes , Salmonella infantis , Salmonella kentucky , and Escherichia coli ) and Gram‐positive bacteria (Staphylococcus aureus , Bacillus subtilis , and Enterococcus durans ) using a disk diffusion method. Moreover, an antifungal activity experiment was performed against Candida albicans using the disk diffusion method. It was observed that the synthesized 1,3,4‐thiadiazole derivatives exhibited effective antimicrobial activity against S. aureus , E. coli , and C. albicans . Based on these results, the 1,3,4‐thiadiazole derivatives can be considered as a source of bioactive agents for pharmacological and medicinal applications.     

Antioxidant and anticancer activities of α-aminophosphonates containing thiadiazole moiety

In the current study, α-aminophosphonates containing thiadiazole moiety (1–4) was synthesized, characterized and their antioxidant and anticancer activities were carried out. The compounds (1–4) were synthesized from the reaction of 2-amino-5-methyl-1,3,4-thiadiazole with various aldehydes, triphenylphosphite and mixed valence Cu(I)/Cu(II) inorganic coordination polymer as a catalyst. The elucidation of compounds structures were carried out using different spectroscopic techniques. The antioxidant properties were carried out using radical scavenging methods (DPPH) which exhibited excellent scavenging activity particularly with compound 3. The cytotoxic effects of the five compounds on the human hepato cellular carcinoma (HepG2) and breast adeno carcinoma (MCF7) cell lines were evaluated using MTT assay which revealed the presence of cytotoxic effect with highest activity for compound 3 on HepG2 and compound 1 on MCF7. This suggests that these five compounds, particularly compounds 1 and 3, have antioxidant and anticancer effect and could be used as novel chemotherapeutic compounds but this needs further in vivo investigation to confirm our in vitro results.