893638-95-4Relevant academic research and scientific papers
Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators
Bi, Fangchao,Song, Di,Zhang, Nan,Liu, Zhiyang,Gu, Xinjie,Hu, Chaoyu,Cai, Xiaokang,Venter, Henrietta,Ma, Shutao
, p. 90 - 103 (2018/10/04)
Antibiotic resistance among clinically significant bacterial pathogens is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. Utilizing computational docking method and structure-based optimization strategy, we rationally designed and synthesized two series of isoxazol-3-yl- and isoxazol-5-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their activity against a panel of Gram-positive and -negative pathogens revealed that compounds B14 and B16 that possessed the isoxazol-5-yl group showed strong antibacterial activity against various testing strains, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. aureus. Further molecular biological studies and docking analyses proved that the compound functioned as an effective inhibitor to alter the dynamics of FtsZ self-polymerization via a stimulatory mechanism, which finally terminated the cell division and caused cell death. Taken together, these results could suggest a promising chemotype for development of new FtsZ-targeting bactericidal agent.
Design, synthesis and biological evaluation of stilbene derivatives as novel inhibitors of protein tyrosine phosphatase 1B
He, Haibing,Ge, Yinghua,Dai, Hong,Cui, Song,Ye, Fei,Jin, Jia,Shi, Yujun
, (2016/12/30)
By imitating the scaffold of lithocholic acid (LCA), a natural steroidal compound displaying Protein Tyrosine Phosphatase 1B (PTP1B) inhibitory activity, a series of stilbene derivatives containing phenyl-substituted isoxazoles were designed and synthesized. The structures of the title compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. Activities of the title compounds were evaluated on PTP1B and the homologous enzyme TCPTP by using a colorimetric assay. Most of the target compounds had good activities against PTP1B. Among them, compound 29 (IC50 = 0.91 ± 0.33 μM), characterized by a 5-(2,3-dichlorophenyl) isoxazole moiety, exhibited an activity about 14-fold higher than the lead compound LCA and a 4.2-fold selectivity over TCPTP. Compound 29 was identified as a competitive inhibitor of PTP1B with a Ki value of 0.78 μM in enzyme kinetic studies.
2-Amino-3-cyano-4-(5-arylisoxazol-3-yl)-4H-chromenes: Synthesis and in vitro cytotoxic activity
Akbarzadeh, Tahmineh,Rafinejad, Ali,Mollaghasem, Javad Malekian,Safavi, Maliheh,Fallah-Tafti, Asal,Pordeli, Mahboobeh,Ardestani, Sussan Kabudanian,Shafiee, Abbas,Foroumadi, Alireza
experimental part, p. 386 - 392 (2012/07/27)
A new series of 4-aryl-4H-chromenes bearing a 5-arylisoxazol-3-yl moiety at the C-4 position were prepared as potential anticancer agents. The in vitro cytotoxic activity of the synthesized compounds was investigated against a panel of tumor cell lines in
MGLUR5 MODULATORS
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Page/Page column 41, (2008/06/13)
The present invention is directed to compounds of formula (I) Wherein R1 to R5, X and Z are further defined in the description. The invention also relates to processes for the preparation of the compounds and to intermediates used in
MGluR5 modulators V
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Page/Page column 14, (2008/06/13)
The present invention is directed to novel compounds, to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds.
