1353735-89-3Relevant academic research and scientific papers
Synthesis and biological evaluation of novel 2-methoxypyridylamino- substituted riminophenazine derivatives as antituberculosis agents
Zhang, Dongfeng,Liu, Yang,Zhang, Chunlin,Zhang, Hao,Wang, Bin,Xu, Jian,Fu, Lei,Yin, Dali,Cooper, Christopher B.,Ma, Zhenkun,Lu, Yu,Huang, Haihong
, p. 4380 - 4394 (2014/05/20)
Clofazimine, a member of the riminophenazine class, is one of the few antibiotics that are still active against multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis). However, the clinical utility of this agent is limited by its undesirable physicochemical properties and skin pigmentation potential. With the goal of maintaining potent antituberculosis activity while improving physicochemical properties and lowering skin pigmentation potential, a series of novel riminophenazine derivatives containing a 2-methoxypyridylamino substituent at the C-2 position of the phenazine nucleus were designed and synthesized. These compounds were evaluated for antituberculosis activity against M. tuberculosis H37Rv and screened for cytotoxicity. Riminophenazines bearing a 3-halogen- or 3,4-dihalogen-substituted phenyl group at the N-5 position exhibited potent antituberculosis activity, with MICs ranging from 0.250.01 μg/mL. The 3,4-dihalogensubstituted compounds displayed low cytotoxicity, with IC50 values greater than 64 μg/mL. Among these riminophenazines, compound 15 exhibited equivalent in vivo efficacy against M. tuberculosis infection and reduced skin discoloration potential in an experimental mouse infection model as compared to clofazimine. Compound 15, as compared to clofazimine, also demonstrated improved physicochemical properties and pharmacokinetic profiles with a short half-life and less drug tissue accumulation. This compound is being evaluated as a potential drug candidate for the treatment of multidrug resistant tuberculosis.
RIMINOPHENAZINES WITH 2-(HETEROARYL)AMINO SUBSTITUENTS AND THEIR ANTI-MICROBIAL ACTIVITY
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Page/Page column 210, (2012/01/15)
The present invention relates to riminophenazines having heteroaromatic substitutions, including those with 2-heteroaryl-amino substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.
