852815-58-8Relevant 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.
SUBSTITUTED PYRAZOLES AS PPAR AGONISTS
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Page/Page column 97-98, (2010/02/12)
A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof (I) wherein: p is O or 1; q is O or 1; R1 and R2 are independently H or C1-3 alkyl; R3 and R4 are independently H, C1-6 alkyl, -OC1-6 alkyl, halogen, OH, C2-6 alkenyl or CF3; R5 is H, C1-6 alkyl (optionally substituted by one or more halogens, -COphenyl, OC1-6 alkyl, phenyl morpholino or C2-6 alkenyl. R6 is C1-6 alkyl, halogen, -OCH2 phenyl, phenyl (optionally substituted by C1-3 alkiyl), morpholino, pyrrolidino, piperidino, thiophenyl, furanyl pyridinyl or -OC2-6 alkenyl. These compounds activate the alpha and gamma subtypes fo the hppar receptor and are useful e.g. in the treatment of diabetes, dyslipidemia or syndrome X.
