- New 1,3,4-oxadiazolecopper(II) derivatives obtained from thiosemicarbazone complexes
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Pyridine-2-carbaldehyde thiosemicarbazone and pyridine-2-carbaldehyde 4N-methyl thiosemicarbazone ligands (HLI and HLImm respectively) undergo an oxidative cyclization when treated with bromate or iodate, leading to 2-amino-5-pyridin
- Gomez-Saiz, Patricia,Garcia-Tojal, Javier,Maestro, Miguel A.,Mahia, Jose,Arnaiz, Francisco J.,Lezama, Luis,Rojo, Teofilo
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- Ultrapotent Inhibitor of Clostridioides difficile Growth, Which Suppresses Recurrence in Vivo
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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.
- Naclerio, George A.,Abutaleb, Nader S.,Li, Daoyi,Seleem, Mohamed N.,Sintim, Herman O.
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p. 11934 - 11944
(2020/11/26)
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- Synthesis of 2-amino-1,3,4-oxadiazoles and 2-Amino-1,3,4-thiadiazoles via sequential condensation and I2-mediated oxidative C-O/C-S bond formation
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2-Amino-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles were synthesized via condensation of semicarbazide/thiosemicarbazide and the corresponding aldehydes followed by I2-mediated oxidative C-O/C-S bond formation. This transition-metal-free sequential synthesis process is compatible with aromatic, aliphatic, and cinnamic aldehydes, providing facile access to a variety of diazole derivatives bearing a 2-amino substituent in an efficient and scalable fashion.
- Niu, Pengfei,Kang, Jinfeng,Tian, Xianhai,Song, Lina,Liu, Hongxu,Wu, Jie,Yu, Wenquan,Chang, Junbiao
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p. 1018 - 1024
(2015/01/30)
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- Structure-activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis
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A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl) -1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 μM or 0.008 μg/mL in 7H9 media and therapeutic index of nearly ～300. However, 55 is rapidly metabolized by human liver microsomes (t1/2 = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of ～10-5.
- Meissner, Anja,Boshoff, Helena I.,Vasan, Mahalakshmi,Duckworth, Benjamin P.,Barry III, Clifton E.,Aldrich, Courtney C.
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p. 6385 - 6397
(2013/10/22)
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- A green approach for the synthesis of biologically active heterocyclic compounds at the platinum electrode
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In the present study, 2-amino-5-substituted-1,3,4-oxadiazoles (4a-k) have been synthesized by the electrochemical oxidation of semicarbazone (3a-k) using platinum anode at room temperature under controlled potential electrolysis in an undivided cell assem
- Sanjeev, Kumar,Srivastava
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p. 1019 - 1026
(2013/09/23)
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- Oxidation of 2-amino-5-aryl-1,3,4-oxadiazole by sodium periodate: A kinetic study
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Kinetics of oxidation of a few 2-amino-5-aryl-1,3,4-oxadiazoles by sodium periodate in aqueous acetic acid-HClO4 medium have been studied. The reaction follows a first order rate each with respect to oxidant and substrate concentration. A suita
- Pradhan, Banasova,Misro,Padhy, Arun Kumar
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p. 898 - 900
(2007/10/03)
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