- Discovery of 1,3,4-oxadiazol-2-one-containing benzamide derivatives targeting FtsZ as highly potent agents of killing a variety of MDR bacteria strains
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The spread of infections caused by multidrug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), has created a need for new antibiotics with novel mechanisms of action. The bacterial division protein FtsZ has been identified as a novel drug target that can be exploited clinically. As part of an ongoing effort to develop FtsZ-targeting antibacterial agents, we describe herein the design, synthesis and bioactivity of six series of novel 1,3,4-oxadiazol-2-one-containing, 1,2,4-triazol-3-one-containing and pyrazolin-5-one-containing benzamide derivatives. Among them, compound A14 was found to be the most potent antibacterial agent, much better than clinical drugs such as ciprofloxacin, linezolid and erythromycin against all the tested gram-positive strains, particularly methicillin-resistant, penicillin-resistant and clinical isolated S. aureus. Subsequent studies on biological activities and docking analyses proved that A14 functioned as an effective compound targeting FtsZ. Preliminary SAR indicated a general direction for further optimization of these novel analogues. Taken together, this research provides a promising chemotype for developing newer FtsZ-targeting bactericidal agents.
- Bi, Fangchao,Song, Di,Qin, Yinhui,Liu, Xingbang,Teng, Yuetai,Zhang, Na,Zhang, Panpan,Zhang, Nan,Ma, Shutao
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p. 3179 - 3193
(2019/06/17)
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- Bis-heterocycles. Part I: Tetrahydro-5,5′- bi(1,2,4-triazin-6-ones)
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Selected sets of tetrahydro-5,5′-bi(1,2,4-triazines) (1-3) appended with acetyl, benzoyl, and ester moieties at C-3 position and N-1 (p-substituted)phenyl ring have been prepared and characterized by spectral (IR, NMR, MS) data and X-ray diffraction for c
- Mohammad, Hanan H.,El-Abadelah, Mustafa M.,Sabri, Salim S.,Awwadi, Firas F.,Voelter, Wolfgang
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p. 965 - 974
(2018/11/23)
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- Design, synthesis, and structure–activity relationship of novel and effective apixaban derivatives as FXa inhibitors containing 1,2,4-triazole/pyrrole derivatives as P2 binding element
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Four series of novel and potent FXa inhibitors possessing the 1,2,4-triazole moiety and pyrrole moiety as P2 binding element and dihydroimidazole/tetrahydropyrimidine groups as P4 binding element were designed, synthesized, and evaluated for their anticoagulant activity in human and rabbit plasma in vitro. Most compounds showed moderate to excellent activity. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human FXa in vitro and rat venous thrombosis in vivo. The most promising compound 14a, with an IC50(FXa) value of 0.15?μM and 99% inhibition rate, was identified for further evaluation as an FXa inhibitor.
- Wang, Yong,Sun, Xiaoqing,Yang, Di,Guo, Zhuang,Fan, Xuxu,Nie, Minhua,Zhang, Feng,Liu, Yue,Li, Yue,Wang, Yulin,Gong, Ping,Liu, Yajing
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p. 5646 - 5661
(2016/10/24)
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- N -(4-cyanotetrahydro-2 H -pyran-4-yl) and N -(1-cyanocyclohexyl) derivatives of 1,5-diarylpyrazole-3-carboxamides showing high affinity for 18 kDa translocator protein and/or cannabinoid receptors
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In order to develop improved radioligands for imaging brain CB1 receptors with positron emission tomography (PET) based on rimonabant (5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl) -1H-pyrazole-3-carboxamide, 1), we synt
- Donohue, Sean R.,Dannals, Robert F.,Halldin, Christer,Pike, Victor W.
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experimental part
p. 2961 - 2970
(2011/06/24)
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- A new method for the synthesis of 1-aryl-1,2,4-triazole derivatives
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A new and convenient one-step recyclization method for the synthesis of ethyl 1-aryl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxylates is reported. Various ethyl chloro(2-arylhydrazinylidene)ethanoates react with thiazolidine-2,4-dione in the presence of potassium hydroxide to produce the 1-aryl-1,2,4-triazole derivatives in moderate to good yields. The procedure is economical, environmentally friendly and simple to perform. Georg Thieme Verlag Stuttgart - New York.
- Matiychuk, Vasyl S.,Potopnyk, Mykhaylo A.,Luboradzki, Roman,Obushak, Mykola D.
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experimental part
p. 1799 - 1803
(2011/07/08)
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