79445-97-9Relevant academic research and scientific papers
Synthesis and biological evaluation of novel pyrazole carboxamide with diarylamine-modi?ed scaffold as potent antifungal agents
Zhang, Xiao-Xiao,Jin, Hong,Deng, Yuan-Jie,Gao, Xu-Heng,Li, Yong,Zhao, Yong-Tian,Tao, Ke,Hou, Tai-Ping
, p. 1731 - 1736 (2017/07/27)
Twenty-seven novel pyrazole carboxamides with diarylamine-modi?ed scaffold were designed, synthesized and characterized in detail via 1H NMR, 13C NMR, IR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. Among them, compound 9c-7 exhibited the highest antifungal activities against R. solani, R. cerealis and S. sclerotiorum in vitro with IC50 values of 0.013, 1.608 and 1.874?μg/mL, respectively. Notably, compound 9c-7 still presented the highest fungicidal activities against R. solani in vivo with an IC50 value of 22.21?μg/mL. Molecular docking simulation results reveal that compound 9c-7 binds well to the hydrophobic pockets of the receptor protein succinate dehydrogenase. This study suggests that compound 9c-7 could act as a potential fungicide to be used for further optimization.
Systematic evaluation of structure-activity relationships of the riminophenazine class and discovery of a C2 pyridylamino series for the treatment of multidrug-resistant tuberculosis
Liu, Binna,Liu, Kai,Lu, Yu,Zhang, Dongfeng,Yang, Tianming,Li, Xuan,Ma, Chen,Zheng, Meiqin,Wang, Bin,Zhang, Gang,Wang, Fei,Ma, Zhenkun,Li, Chun,Huang, Haihong,Yin, Dali
experimental part, p. 4545 - 4559 (2012/07/01)
Clofazimine, a member of the riminophenazine class of drugs, is the cornerstone agent for the treatment of leprosy. This agent is currently being studied in clinical trials for the treatment of multidrug-resistant tuberculosis to address the urgent need for new drugs that can overcome existing and emerging drug resistance. However, the use of clofazimine in tuberculosis treatment is hampered by its high lipophilicity and skin pigmentation side effects. To identify a new generation of riminophenazines that is less lipophilic and skin staining, while maintaining efficacy, we have performed a systematic structure-activity relationship (SAR) investigation by synthesizing a variety of analogs of clofazimine and evaluating their anti-tuberculosis activity. The study reveals that the central tricyclic phenazine system and the pendant aromatic rings are important for anti-tuberculosis activity. However, the phenyl groups attached to the C2 and N5 position of clofazimine can be replaced by a pyridyl group to provide analogs with improved physicochemical properties and pharmacokinetic characteristics. Replacement of the phenyl group attached to the C2 position by a pyridyl group has led to a promising new series of compounds with improved physicochemical properties, improved anti-tuberculosis potency, and reduced pigmentation potential.
