5711-61-5Relevant academic research and scientific papers
Synthesis and anticonvulsant evaluation of indoline derivatives of functionalized aryloxadiazole amine and benzothiazole acetamide
Akhtar, Md Jawaid,Debnath, Biplab,Grover, Gourav,Nath, Rajarshi,Pathania, Shelly,Shahar Yar, M.
, (2020/12/25)
A series of N-(substituted benzothiazole-2-yl)-2-(2,3-dioxoindolin-1-yl)acetamide (4a-i) and substituted-[3-((5-phenyl-1,3,4-oxadiazole-2-yl)imino)indolene-2-one] (5a-f) were designed, synthesized fulfilling the structural requirement of pharmacophore and evaluated for anticonvulsant activities using maximal electroshock test (MES), subcutaneous pentylenetetrazole (scPTZ) seizures and neurotoxicity by motor impairment model in mice. The most active compoundN-(5-chlorobenzo[d]thiazol-2-yl)-2-(2,3-dioxoindolin-1-yl)acetamide (4a) has shown significant anticonvulsant activity against both MES and scPTZ screens and emerged as most effective anticonvulsant compound with median dose of 35.7 mg/kg (MES ED50), 88.15 mg/kg (scPTZ ED50) and toxic dose (TD50) was found to be > 500mg/kg. In silico studies including molecular docking study was carried to establish the molecular interaction of potent compound (4a) in both Na+ channel and GABAA receptors. The prediction of pharmacokinetic parameters and distance mapping of compounds were also performed to establish the drug likeness property.
Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety
Han, Xu,Liu, Xin Hua,Ma, Duo,Yu, Yun Long,Zhang, Zhao Yan
, p. 344 - 360 (2021/01/06)
Based on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC50 50 = 6.41 μM). In addition, clear structure–activity relationships were summarised, indicating that the substitution of the methoxy group and the position, type and number of the substituents on the phenyl ring had significant effects on telomerase activity. Among them, compound A33 showed considerable inhibition against telomerase. Flow cytometric analysis showed that compound A33 could arrest MGC-803 cell cycle at G2/M phase and induce apoptosis in a concentration-dependent way. Meanwhile, Western blotting revealed that this compound could reduce the expression of dyskerin, which is a fragment of telomerase.
SSAO INHIBITOR
-
, (2020/04/02)
The present invention provides an SSAO inhibitor and an application thereof in preparing a drug for treating a disease related to SSAO. In particular, the present invention provides a compound shown in formula (IV) and a pharmaceutically acceptable salt thereof.
Ultrapotent Inhibitor of Clostridioides difficile Growth, Which Suppresses Recurrence in Vivo
Naclerio, George A.,Abutaleb, Nader S.,Li, Daoyi,Seleem, Mohamed N.,Sintim, Herman O.
, p. 11934 - 11944 (2020/11/26)
Clostridioides difficile is the leading cause of healthcare-associated infection in the U.S. and considered an urgent threat by the Centers for Disease Control and Prevention (CDC). Only two antibiotics, vancomycin and fidaxomicin, are FDA-approved for the treatment of C. difficile infection (CDI), but these therapies still suffer from high treatment failure and recurrence. Therefore, new chemical entities to treat CDI are needed. Trifluoromethylthio-containing N-(1,3,4-oxadiazol-2-yl)benzamides displayed very potent activities [sub-μg/mL minimum inhibitory concentration (MIC) values] against Gram-positive bacteria. Here, we report remarkable antibacterial activity enhancement via halogen substitutions, which afforded new anti-C. difficile agents with ultrapotent activities [MICs as low as 0.003 μg/mL (0.007 μM)] that surpassed the activity of vancomycin against C. difficile clinical isolates. The most promising compound in the series, HSGN-218, is nontoxic to mammalian colon cells and is gut-restrictive. In addition, HSGN-218 protected mice from CDI recurrence. Not only does this work provide a potential clinical lead for the development of C. difficile therapeutics but also highlights dramatic drug potency enhancement via halogen substitution.
Synthesis of N-pyrimidin[1,3,4]oxadiazoles and N-pyrimidin[1,3,4]-thiadiazoles from 1,3,4-oxadiazol-2-amines and 1,3,4-thiadiazol-2-amines via Pd-catalyzed heteroarylamination
Yan, Longjia,Deng, Minggao,Chen, Anchao,Li, Yongliang,Zhang, Wanzheng,Du, Zhi-yun,Dong, Chang-zhi,Meunier, Bernard,Chen, Huixiong
supporting information, p. 1359 - 1362 (2019/04/25)
An efficient and practical procedure was developed to prepare various N-pyrimidin[1,3,4]oxadiazole and thiadiazole scaffolds using a Buchwald-type coupling. The products of this reaction are otherwise difficult to access and could be used as building bloc
Efficient synthesis of novel conjugated 1,3,4-oxadiazole-peptides
Golmohammadi, Farhad,Balalaie, Saeed,Hamdan, Fatima,Maghari, Shokoofeh
, p. 4344 - 4351 (2018/03/21)
We were interested in the design and synthesis of novel bioisosteric analogues of leuprolide acetate containing the oxadiazole moiety at the C- or N-terminal of the peptide. An efficient approach for the synthesis of 2-amino-1,3,4-oxadiazoles through the reaction of hydrazide with ammonium thiocyanate and desulfurization reaction of the thiosemicarbazides using different coupling reagents was employed. These compounds are bioisosteres of the amide bond. Furthermore, the coupling of 2-amino-1,3,4-oxadiazoles at the C-terminal of leuprolide analogues was carried out, using a coupling reagent in the solution phase. On the other hand, the addition of a 2-amino-1,3,4-oxadiazole to the N-terminal of the peptide sequence was carried out through the reaction of the 2-amino-1,3,4-oxadiazole with succinic anhydride that led to the formation of a carboxylic acid moiety. Addition of the synthesized oxadiazole containing carboxylic acid to the peptide sequence was performed using a coupling reagent and on the surface of the resin. The synthesized peptides containing the oxadiazole moiety at the C- or N-terminal of the peptide sequence are peptidomimetics of leuprolide acetate. All of the synthesized peptides were purified using preparative HPLC and their structures were confirmed using HR-MS (ESI).
Spiro-heterocycles containing 1,3,4-oxadiazole: A convenient synthesis of 3-(5- Substitutedphenyl-l,3,4-oxadiazole-2-yl)-5,8-dithiaspiro[3,4]-octan-2-onesand 1,4-dithia-6-azaspiro[4,4]-nonan-7-ones
Tiwari, Shailendra,Singh, Kamal Pratap,Pathak, Poonam,Ahmad, Akeel
, p. 1060 - 1064 (2019/05/22)
A new series of novel 3-(5-substituted phenyl-l,3,4-oxadiazole-2-yl)-5,8-dithiaspiro [3,4]-octan-2-ones and l,4-dithia-6- azaspiro[4,4]nonan-7-ones have been synthesized from a common intermediate, in good yields. These compounds have been screened for th
Design, synthesis, and biological activity of novel tetrahydropyrazolopyridone derivatives as FXa inhibitors with potent anticoagulant activity
Sun, Xiaoqing,Hong, Zexin,Liu, Moyi,Guo, Su,Yang, Di,Wang, Yong,Lan, Tian,Gao, Linyu,Qi, Hongxia,Gong, Ping,Liu, Yajing
, p. 2800 - 2810 (2017/04/18)
A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b, 15c, 20b, 20c, and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c, with an IC50 (FXa) value of 0.14?μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor.
Ultrasound-assisted synthesis of 2-amino-1,3,4-oxadiazoles through NBS-mediated oxidative cyclization of semicarbazones
Borsoi, Ana Flávia,Coldeira, Mateus Emanuel,Pissinate, Kenia,Macchi, Fernanda Souza,Basso, Luiz Augusto,Santos, Diógenes Santiago,Machado, Pablo
, p. 1319 - 1325 (2017/07/12)
A ultrasound-assisted oxidative cyclization of semicarbazones using N-bromosuccinimide in the presence of sodium acetate was established providing efficient and rapid access to a variety of 2-amino-1,3,4-oxadiazoles. Moreover, the new synthetic protocol provides a simple procedure utilizing a safer oxidizing system that affords the target products in high regioselectivity, satisfactory yields, and elevated purities.
Inhibitors of ribosome rescue arrest growth of francisella tularensis at all stages of intracellular replication
Goralski, Tyler D. P.,Dewan, Kalyan K.,Alumasa, John N.,Avanzato, Victoria,Place, David E.,Markley, Rachel L.,Katkere, Bhuvana,Rabadi, Seham M.,Bakshi, Chandra Shekhar,Keiler, Kenneth C.,Kirimanjeswara, Girish S.
supporting information, p. 3276 - 3282 (2016/07/06)
Bacteria require at least one pathway to rescue ribosomes stalled at the ends of mRNAs. The primary pathway for ribosome rescue is trans-translation, which is conserved in >99% of sequenced bacterial genomes. Some species also have backup systems, such as ArfA or ArfB, which can rescue ribosomes in the absence of sufficient trans-translation activity. Small-molecule inhibitors of ribosome rescue have broad-spectrum antimicrobial activity against bacteria grown in liquid culture. These compounds were tested against the tier 1 select agent Francisella tularensis to determine if they can limit bacterial proliferation during infection of eukaryotic cells. The inhibitors KKL-10 and KKL-40 exhibited exceptional antimicrobial activity against both attenuated and fully virulent strains of F. tularensis in vitro and during ex vivo infection. Addition of KKL-10 or KKL-40 to macrophages or liver cells at any time after infection by F. tularensis prevented further bacterial proliferation. When macrophages were stimulated with the proinflammatory cytokine gamma interferon before being infected by F. tularensis, addition of KKL-10 or KKL-40 reduced intracellular bacteria by >99%, indicating that the combination of cytokine-induced stress and a nonfunctional ribosome rescue pathway is fatal to F. tularensis. Neither KKL-10 nor KKL-40 was cytotoxic to eukaryotic cells in culture. These results demonstrate that ribosome rescue is required for F. tularensis growth at all stages of its infection cycle and suggest that KKL-10 and KKL-40 are good lead compounds for antibiotic development.
