565174-22-3Relevant academic research and scientific papers
Novel 1,2,4-Triazole Compound And Pharmaceutical Composition For Inhibiting Urease Comprising The Same
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, (2019/09/12)
The present invention provides a 1,2,4-triazole compound represented by formula 1 or a pharmaceutically acceptable salt thereof: In formula 1, R is a methoxy group, a fluoro or bromo group, Y is a thiophenyl group, a pyroyl group, an ethyl phenyl group, a
Synthesis, biological activities and SAR studies of new 3-substitutedphenyl-4-substitutedbenzylideneamino-1,2,4-triazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors
Wang, Bao-Lei,Zhang, Li-Yuan,Liu, Xing-Hai,Ma, Yi,Zhang, Yan,Li, Zheng-Ming,Zhang, Xiao
, p. 5457 - 5462 (2017/11/17)
A series of new 3-substitutedphenyl-4-substitutedbenzylideneamino-1,2,4-triazole Mannich bases and bis-Mannich bases were synthesized through Mannich reaction with high yields. Their structures were confirmed by means of IR, 1H NMR, 13C NMR and elemental analysis. The preliminary bioassay indicated that compounds 7g, 7h and 7l exhibited potent in vitro inhibitory activities against ketol-acid reductoisomerase (KARI) with Ki value of (0.38 ± 0.25), (6.59 ± 2.75) and (8.46 ± 3.99) μmol/L, respectively, and were comparable with IpOHA. They could be new KARI inhibitors for follow-up research. Some of the title compounds also exhibited obvious herbicidal activities against Echinochloa crusgalli and remarkable in vitro fungicidal activities against Physalospora piricola and Rhizoctonia cerealis. The SAR of the compounds were analyzed, in which the molecular docking revealed the binding mode of 7g with the KARI, and the 3D-QSAR results provided useful information for guiding further optimization of this kind of structures to discover new fungicidal agents towards Rhizoctonia cerealis.
Synthesis and biological activities of 3,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivatives
Lin, Lu,Liu, Hua,Wang, Dun-Jia,Hu, Yan-Jun,Wei, Xian-Hong
, p. 481 - 489 (2018/02/06)
Twelve novel triazolothiadiazole derivatives were synthesized from 4-amino-5-substituted-4H-1,2,4-triazole-3-thiols with various aromatic carboxylic acids by cyclization in the presence of phosphorous oxychloride. All the newly synthesized compounds were characterized by FTIR, 1H NMR, mass spectroscopy and elemental analysis. The antimicrobial activities of the title compounds were examined by disc diffusion method against Escherichia coli, Staphylococcus aureus, Pyricularia oryzae and Rhizoctnia solani. The bioassay indicated all synthesized triazolothiadiazole derivatives possessed moderate to good antibacterial and antifungal activities against the tested organisms. Especially, compounds 2e and 2k exhibited excellent antibacterial and antifungal activities among these triazolothiadiazole derivatives.
Facile synthesis, biological evaluation and molecular docking studies of novel substituted azole derivatives
Rafiq, Muhammad,Saleem, Muhammad,Jabeen, Farukh,Hanif, Muhammad,Seo, Sung-Yum,Kang, Sung Kwon,Lee, Ki Hwan
, p. 177 - 191 (2017/03/15)
In this study, we synthesized the series of novel azole derivatives and evaluated for enzyme inhibition assays, corresponding kinetic analysis and molecular modeling. Among the investigated bioassays, the oxadiazole derivatives 4a-k were found potent α-glucosidase inhibitors while the Schiff base derivatives 7a-k exhibited considerable potential toward urease inhibition. The inhibition kinetics for the most active compounds were analyzed by the Lineweaver–Burk plots to investigate the possible binding modes of the synthesized compounds toward the tested proteins. Moreover, the detailed docking studies were performed on the synthesized library of 4a-k and 7a-k to study the molecular interaction and binding mode in the active site of the modeled yeast α-glucosidase and Jack Bean Urease, respectively. It could be inferred from docking results that theoretical studies are in close agreement to that of the experimental results. The structure of one of the compound 7k was characterized by the single crystal X-ray diffraction analysis in order to find out the predominant conformation of the molecules.
1,2,4-Triazolethione derivative containing (hetero)aryl group and piperazine, and preparation method and application thereof
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, (2016/10/07)
The invention discloses a 1,2,4-triazolethione derivative containing a (hetero)aryl group and piperazine, and a preparation method and an application thereof. The synthesis method has the advantages of few reaction steps, simple and mild conditions, simple operation and high yield. The derivative has a structural formula represented by general formula I and general formula II, and R, R and R in the general formula I and the general formula II are as defined in claim 1. The above compounds have certain in vitro inhibition activity to cucumber fusarium wilt, Cercospora arachidicola Hori, Macrophoma kawatsukai, Altemaria solani, Fusarium graminearum, Rhizoctonia cerealis and other plant pathogens, and especially have high in vitro inhibition activity on the cucumber fusarium wilt, Cercospora arachidicola Hori, Macrophoma kawatsukai and Rhizoctonia cerealis. The compounds of the general formula I and general formula II simultaneously have rice KARI enzyme in vitro inhibition activity. The derivative is suitable for comprehensive control of fungus damages on various crops.
Synthesis, anti-HIV activity and Molecular modeling study of 3-aryl-6-adamantylmethyl-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazole derivatives
Khan, Mahmood-Ul-Hassan,Hameed, Shahid,Farman, Muhammad,Al-Masoudia, Najim A.,Stoeckli-Evans, Helen
, p. 609 - 616 (2016/02/18)
A series of novel 3-aryl-6-adamantylmethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 6a-l were synthesized by a simple method with the aim of developing novel HIV non-nucleoside reverse transcriptase inhibitors. All the synthesized compounds were structurally confirmed by spectral analyses. The structure of 6a was unambiguously verified by X-ray structure determination. The synthesized compounds were evaluated for their anti-HIV activity and four analogs displayed moderate inhibitory activity with EC50 values ranging from 10.10 to 12.40 μg mL-1. Molecular docking of 6g with HIV-1 reverse transcriptase was studied to rationalize some structureactivity relationships (SARs).
Design, synthesis, and urease inhibition studies of a series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones
Khan, Mahmood-Ul-Hassan,Hameed, Shahid,Yasin, Khawaja A.,Akhtar, Tashfeen,Khan, Khalid M.
experimental part, p. 479 - 484 (2011/08/03)
A series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones was synthesized by reaction of aryl hydrazides with CS2 and hydrazine hydrate. The synthesized compounds were characterized by spectroanalytical techniques, and their urease inhibition activity was evaluated using jack bean urease. All but one of the synthesized compounds were active, and two of them were found to be more potent than the standard, with 50% inhibition concentration (IC 50) values of 17.5 ± 0.52 and 4.3 ± 0.169 μM, respectively (standard IC 50 = 21.0 ± 0.11 μM). Tentative statements regarding the role of different functional groups in binding to the enzyme active site are also presented.
Synthesis, crystal structure and antiproliferative activity of 6-adamantyl-3-aryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles
Khan, Mahmood-Ul-Hassan,Akhtar, Tashfeen,Yasin, Khawaja A.,Al-Masoudi, Najim A.,Jones, Peter G.,Hameed, Shahid
scheme or table, p. 178 - 184 (2010/08/22)
A series of 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a - l bearing an adamantyl moiety were synthesized by condensation of 4-amino-5-aryl-2H-1,2,4-triazole-3(4H)-thiones 4a - l with adamantyl-1- carboxylic acid in the presence of POCl3. The structures of the newly synthesized compounds were established using spectroanalytical techniques and verified further by the crystal structure determination of compounds 5a and 5j. The compounds were screened for their antiproliferative activity against a large panel of human cell lines.
Novel lead structures for p38 MAP kinase via FieldScreen virtual screening
Cheeseright, Timothy J.,Holm, Melanie,Lehmann, Frank,Luik, Sabine,Gottert, Marcia,Melville, James L.,Laufer, Stefan
experimental part, p. 4200 - 4209 (2010/01/16)
p38 MAP kinase has received considerable interest in the pharmaceutical industry and remains a valid and interesting target for the treatment of inflammation. To discover novel p38 inhibitors, we applied the ligand-based virtual screening technique, FieldScreen, to 1.2 million commercially available compounds. Fifty-eight diverse compounds were selected for biological analysis, using molecular field similarity to known inhibitors, while explicitly removing any structure that shared a scaffold with previously reported p38 inhibitors. Of these, 11 (19%) showed ≥20% inhibition of p38 at 10 μM. We chose to prepare analogues of two distinct chemical series resulting in a potential lead compound with pIC50 of 6.4. Modeling of SAR using FieldAlign, a ligand alignment protocol, was used to rationalize the SAR of the series of thiadiazole based inhibitors.
Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors
Skoumbourdis, Amanda P.,LeClair, Christopher A.,Stefan, Eduard,Turjanski, Adrian G.,Maguire, William,Titus, Steven A.,Huang, Ruili,Auld, Douglas S.,Inglese, James,Austin, Christopher P.,Michnick, Stephen W.,Xia, Menghang,Thomas, Craig J.
supporting information; experimental part, p. 3686 - 3692 (2010/03/24)
An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively.
