83303-98-4Relevant academic research and scientific papers
Novel dual inhibitors against FP-2 and PfDHFR as potential antimalarial agents: Design, synthesis and biological evaluation
Chen, Wenhua,Yao, Xue,Huang, Zhenghui,Mao, Fei,Guan, Longfei,Tang, Yun,Jiang, Hualiang,Li, Jian,Huang, Jin,Jiang, Lubin,Zhu, Jin
supporting information, p. 250 - 254 (2018/04/05)
Resistance to malaria parasites has quickly developed to almost all used antimalarial drugs. Cysteine protease falcipain-2 (FP-2) and Plasmodium falciparum dihydrofolate reductase (PfDHFR) have crucial roles, which are absolutely necessary, in the parasite life cycle. In this study, based on the uniform pharmacophores of reported PfDHFR inhibitors and the first-generation dual inhibitors against FP-2 and PfDHFR, we identified a novel series of dual inhibitors through fragments assembly. Lead optimization led to the identification of 14, which showed potent inhibition against FP-2 and PfDHFR enzyme (IC50 = 6.8 ± 1.8 μmol/L and IC50 = 8.8 ± 0.3 μmol/L) and P. falciparum 3D7 strain (IC50 = 2.9 μmol/L). Additionally, 14 exhibited more potent inhibition to the proliferation of chloroquine-resistant P. falciparum Dd2 strain (IC50 = 1.1 μmol/L) than pyrimethamine (IC50 > 10 μmol/L), and 14 displayed micromolar inhibitory activities against two clinical isolated strains Fab9 (IC50 = 2.6 μmol/L) and GB4 (IC50 = 1.0 μmol/L). Collectively, these data demonstrated that 14 might be a good lead compound for the treatment of malaria.
AMIDINE DERIVATIVES WITH NITRIC OXIDE SYNTHETASE ACTIVITIES
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, (2008/06/13)
Amidine derivative compounds of formula I as defined in the Specification having nitric oxide synthetase inhibitory activity as well as processes for the preparation of and compositions containing said compounds are described
Synthesis and Photo-oxygenation of Some Substituted 1-Benzyl-3,4-dihydroisoquinolines. Mechanism of Enamine Photo-oxygenation
Martin, Ned H.,Jefford, Charles W.
, p. 762 - 774 (2007/10/02)
The synthesis of a series of substituted 1-benzyl-3,4-dihydroisoquinolines by Bischler-Napieralski cyclization is described.Competitive methylene blue sensitized photo-oxygenation experiments allowed the determination of relative rates of photo-oxygenation of 1-benzyl-3,4-dihydroisoquinolines.Substituents were shown to affect both the equilibrium concentration of the tautomeric enamine and the overall photo-oxygenation rate.After correcting for differences in enamine concentration, the relative rate data provided a diagnostic probe of the reaction mechanism, which involves transfer of charge in the rate-limiting step.
