29313-28-8Relevant academic research and scientific papers
1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-β-lactamases
Sevaille, Laurent,Gavara, Laurent,Bebrone, Carine,De Luca, Filomena,Nauton, Lionel,Achard, Maud,Mercuri, Paola,Tanfoni, Silvia,Borgianni, Luisa,Guyon, Carole,Lonjon, Pauline,Turan-Zitouni, Gülhan,Dzieciolowski, Julia,Becker, Katja,Bénard, Lionel,Condon, Ciaran,Maillard, Ludovic,Martinez, Jean,Frère, Jean-Marie,Dideberg, Otto,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
, p. 972 - 985 (2017/06/27)
Metallo-β-lactamases (MBLs) cause resistance of Gram-negative bacteria to β-lactam antibiotics and are of serious concern, because they can inactivate the last-resort carbapenems and because MBL inhibitors of clinical value are still lacking. We previously identified the original binding mode of 4-amino-2,4-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione (compound IIIA) within the dizinc active site of the L1 MBL. Herein we present the crystallographic structure of a complex of L1 with the corresponding non-amino compound IIIB (1,2-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione). Unexpectedly, the binding mode of IIIB was similar but reverse to that of IIIA. The 3 D structures suggested that the triazole–thione scaffold was suitable to bind to the catalytic site of dizinc metalloenzymes. On the basis of these results, we synthesized 54 analogues of IIIA or IIIB. Nineteen showed IC50 values in the micromolar range toward at least one of five representative MBLs (i.e., L1, VIM-4, VIM-2, NDM-1, and IMP-1). Five of these exhibited a significant inhibition of at least four enzymes, including NDM-1, VIM-2, and IMP-1. Active compounds mainly featured either halogen or bulky bicyclic aryl substituents. Finally, some compounds were also tested on several microbial dinuclear zinc-dependent hydrolases belonging to the MBL-fold superfamily (i.e., endonucleases and glyoxalase II) to explore their activity toward structurally similar but functionally distinct enzymes. Whereas the bacterial tRNases were not inhibited, the best IC50 values toward plasmodial glyoxalase II were in the 10 μm range.
Design and Synthesis of 1,2,4-Triazolo[3,2-b]-1,3,5-thiadiazine Derivatives as a Novel Template for Analgesic/Anti-Inflammatory Activity
Sert-Ozgur, Seyma,Tel, Banu C.,Somuncuoglu, Elif I.,Kazkayasi, Inci,Ertan, Mevlut,Tozkoparan, Birsen
, (2017/07/11)
Previously, we demonstrated that certain heterocyclic compounds derived from 3-substituted-1,2,4-triazole-5-thiones had promising analgesic/anti-inflammatory activities together with low ulcerogenic properties. Therefore, we sought to design and synthesize new derivatives of triazol-5-thiones-fused heterocycles. In the present study, a series of novel bis-Mannich bases, namely 2,6-disubstituted-6,7-dihydro-5H-1,2,4-triazolo[3,2-b]-1,3,5-thiadiazines (1a–d, 2a–c, and 3a–d), were synthesized and characterized to assess their possible anti-inflammatory/analgesic properties. Additionally, their ability to induce gastric toxicity was also evaluated. Several of the condensed compounds produced a degree of analgesic activity comparable to reference drugs in both the hot plate and tail-flick tests. A strong anti-inflammatory effect was observed for the derivatives carrying a benzyl group at the second position (2a–c). The majority of the prepared compounds caused comparatively less gastrointestinal (GI) side effects than the reference drugs naproxen and indomethacin did. These results showed that 1,2,4-triazolo[3,2-b]-1,3,5-thiadiazine derivatives might afford a safer alternative to currently available analgesic/anti-inflammatory agents for the treatment and management of inflammatory disease and pain.
An efficient nonconventional glycerol-based solid acid catalyzed synthesis and biological evaluation of phosphonate conjugates of 1,2,4-triazole thiones
Murty, Madugula S.R.,Katiki, Mohana R.,Rao, Busam R.,Narayanan, Sai S.,Anto, Ruby J.,Buddana, Sudhreer K.,Prakasham, Reddy S.,Devi, Bethala L.A.P.,Prasad, Rachapudi B.N.
, p. 968 - 981 (2016/10/31)
A series of diethyl (3-((5-aryl-1H-1,2,4-triazol-3-yl)thio)propyl)phos-phonates (7a-t) has been synthesized in excellent yields by coupling diethyl (3-bromopropyl)phosphonate and 5-aryl-1H- 1,2,4-triazol-3-thiones employing an efficient, green and nonconventional heterogeneous SO3Hcarbon catalyst derived from glycerol. In addition, a facile and green approach for the esterification of carboxylic acids by utilizing glycerol-based solid acid catalyst has been reported. Structures of the synthesized compounds were characterized by IR, NMR and HRMS studies. These triazole derivatives were screened for their in vitro cytotoxicity using the standard MTT (3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetra-zolium bromide) assay against a panel of five different human cancer cell lines (HeLa: Cervix, A549: Lung, A375: Skin, MDA-MB-231: Breast and T98G: Brain). The antimicrobial activities of the synthesized compounds were investigated against four bacterial strains: Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and three fungal strains: Aspergillus Niger, Aspergillus terreus, Aspergillus fumigatus. Preliminary results indicate that the compound 7f displayed maximum anticancer activity and the compounds 7d, 7e, 7f, 7m and 7q exhibited moderate antibacterial activity. The compounds 7g, 7h, 7o and 7p showed good antifungal activity with high inhibition zone diameter compared to the standard drug.
Synthesis, characterization, and anticancer studies of S and N alkyl piperazine-substituted positional isomers of 1,2,4-triazole derivatives
Murty,Ram, Kesur R.,Rao, B. Ramalingeswara,Rao, Rayudu Venkateswara,Katiki, Mohana Rao,Rao, Janapala Venkateswara,Pamanji,Velatooru
, p. 1661 - 1671 (2014/05/06)
A series of 3-[3-[4-(substituted)-1-cyclicamine] propyl]thio-5- substituted[1,2,4]triazoles (8a-m) and 2-[3-[4-(substituted)-1-cyclicamine] propyl]-5-(substituted)-2,4-dihydro-3H[1,2,4]triazole-3-thiones (9a-h) were synthesized with good yields starting from corresponding carboxylic acids using two different methods. The cytotoxicity studies of these derivatives were studied against five different human cancer cell lines. Six compounds had shown good anticancer activity. The triazole derivatives, 9d, 8j, and 8i were most potent particularly against U937 and HL-60 cells. The cytotoxic potency of the compounds varied between the cell lines suggesting that a structural property of these compounds as possible determinant of their biological activity. Springer Science+Business Media 2013.
Synthesis of new S-alkylated-3-mercapto-1,2,4-triazole derivatives bearing cyclic amine moiety as potent anticancer agents
Murty,Ram, Kesur R.,Rao, Rayudu Venkateswara,Yadav,Rao, Janapala Venkateswara,Pamanji,Velatooru
experimental part, p. 276 - 281 (2012/06/18)
A series of 3-[3-[4-(Substituted)-1-cyclicamine]propyl]thio-5- substituted[1,2,4]triazoles (8a-j) were synthesized with good yields starting from corresponding carboxylic acids. The cytotoxicity studies of these derivatives were studied against five different human cancer cell lines. Three compounds had shown good anticancer activity. The triazole derivatives, 8i and 8j were most potent particularly against U937 and HL-60 cells. The cytotoxic potency of the compounds varied between the cell lines suggesting that a structural property of these compounds as possible determinants of their biological activity.
Efficient synthesis of antifungal active 9-substituted-3-aryl-5H,13aH- quinolino[3,2-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines in ionic liquids
Gupta, Monika
scheme or table, p. 4919 - 4923 (2011/09/16)
The title compounds, 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4] triazolo[4,3-b][1,2,4]triazepines 8, are synthesized from 5-aryl-3,4-diamino-1, 2,4-triazoles 5 and 2-chloro-3-formylquinolines 7 in ionic liquid as solvent under microwave heating as well as using oil-bath heating at 80 °C. The products are obtained in the good to moderate yields and in high purity. These compounds have been screened for antifungal activity. The screening data indicate that the compounds 8a, 8b, 8c and 8d show excellent activity against Aspergillus niger 1000 μg concentration and Pencillium notatum species at 500 μg as well as 1000 μg concentrations whereas, these compounds show good to moderate activity against Aspergillus flavus and Rhizopus species at both the concentrations. Moreover, ionic liquid is found to be recyclable for at least three consecutive runs what makes the process cost-effective and economic that lead to the area of Green Chemistry as recyclability is one of the most important feature of Green Chemistry.
One-pot synthesis of antifungal active 9-substituted-3-aryl-5H,13aH- quinolino [3,2-/][1,2,4]triazolo [4,3-b] [1,2,4]triazepines
Gupta, Monika,Paul, Satya,Gupta, Rajive
scheme or table, p. 475 - 481 (2010/10/03)
The title compounds, 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4] triazolo[4,3-b][1,2,4]triazepines 8, are synthesized from 5-aryl-3,4-diamino-1, 2,4-triazoles 5 and 2-chloro-3-formylquinolines 7 using catalytic amount of p-TsOH and N,N-dimethylformamide as an energy transfer medium using microwave heating as well as solvent using oil-bath heating at 80°C affords novel 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4]triazolo[4,3-b][1,2,4] triazepines. The products are obtained in good to moderate yields and are in a state of high purity.
THIADIAZOLE DERIVATIVES, INHIBITORS OF STEAROYL-COA DESATURASE
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Page/Page column 52, (2008/12/07)
The present invention relates to substituted thiadiazole compounds of the formula (I) and pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds for modulating SCD activity.
Synthesis and antifungal activity of novel 3,6-diaryl-5H-[1,2,4]triazolo[4, 3-b][1,2,4]triazepines
Gupta, Monika
, p. 1023 - 1027 (2008/03/29)
(Chemical Equation Presented) 5-Aryl-3,4-diamino-1,2,4-triazoles 5 on treatment with β-chlorocinnamaldehydes 7 in the presence of catalytic amount of p-TsOH and N,N-dimethylformamide as an energy transfer medium under microwave irradiation and as solvent with oil-bath heating at 80°C affords novel 3,6-diaryl-5H-[1,2,4]triazolo[4,3-b]-1,2,4]triazepines 8. The structures of the synthesized compounds were established on the basis of 1H NMR, IR, mass spectral data and elemental analysis.
