464913-83-5Relevant academic research and scientific papers
Design, synthesis and biological evaluation of diamino substituted cyclobut-3-ene-1,2-dione derivatives for the treatment of drug-resistant tuberculosis
Fu, Lei,Huang, Haihong,Li, Gang,Li, Peng,Lin, Ziyun,Lu, Yu,Wang, Bin,Zhang, Dongfeng
, (2020)
Mycobacterium tuberculosis (Mtb) ATP synthase is an important target for treating drug-resistant infections and sterilizing the bacteria, spurring intensive efforts to develop new TB therapeutics based on this target. In this work, four novel series including furan-2(5H)-ketone (3, 4), maleimide (5) and squaramide (6) derivatives were designed, respectively, through the strategy of scaffold morphing and hydrogen-bond introduction, using the selective Mtb ATP synthase inhibitor compound 2 as the lead compound. The result demonstrated that diamino substituted cyclobut-3-ene-1,2-dione compounds 6ab and 6ah displayed good to excellent in vitro anti-TB activities (MIC 0.452–0.963 μg/mL) with low cytotoxicity (IC50 > 64 μg/mL). In addition, not only did compound 6ab show effective activity against clinically isolated resistant strains, it also revealed good druggability profiles including improved metabolic stability, no hERG channel inhibition potential, and acceptable oral bioavailability. The preliminary result of docking study and in vitro anti-bedaquiline-resistant strain test compared to compound 2 suggested that Mtb ATP synthase is most likely the target of compound 6ab. The structure-activity relationship laid a good foundation for the identification of novel squaramides as a potential treatment of drug-resistant tuberculosis.
TRIAMINOPYRIMIDINE CYCLOBUTENEDIONE DERIVATIVES USED AS PHOSPHATASE CDC25 INHIBITORS
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Page/Page column 15, (2010/07/10)
The present invention relates to triaminopyrimidine derivatives of formula (I) where Y, R3, W, R4a, R5a, R4b, R5b, n and m are variable. These compounds have CDC25 phosphatase-inhibiting activity and can therefore be used as drugs in diseases in which CDC
