- Design and synthesis of novel hydroxypyridinone derivatives as potential tyrosinase inhibitors
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Two groups of novel hydroxypyridinone derivatives 6(a-e) and 12(a-c), were designed as potential tyrosinase inhibitors, and synthesized using kojic acid as a starting material. The tyrosinase inhibitory activity of these two groups was demonstrated to be potent, especially compounds 6e and 12a, whose IC50 values for monophenolase activity were 1.95 μM and 2.79 μM, respectively. Both of these values are lower than that of kojic acid (IC50 = 12.50 μM). Compounds 6e and 12a were investigated for the inhibitory effect on diphenolase activity. The results showed that the inhibitory mechanism of these two compounds was reversible and that the inhibitory type was a competitive-uncompetitive mixed-type. The values of IC50 of 6e and 12a on the diphenolase activity of tyrosinase were determined to be 8.97 μM and 26.20 μM, respectively. The inhibitory constants (KI and KIS) of 6e were determined as 17.17 μM and 22.09 μM, respectively; and the KI and KIS values of 12a were 34.41 μM and 79.02 μM, respectively. Compound 6e showed a greater ability to reduce copper and a stronger copper chelating ability than kojic acid.
- Zhao, De-Yin,Zhang, Ming-Xia,Dong, Xiao-Wu,Hu, Yong-Zhou,Dai, Xiao-Yan,Wei, Xiaoyi,Hider, Robert C.,Zhang, Jin-Chao,Zhou, Tao
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p. 3103 - 3108
(2016/06/13)
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- Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine- 4(1H)-one
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The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the evaluation of its coordination ability towards Fe3+, studied by a combination of chemical, computational, and animal approaches. The use of complementary analytical techniques has allowed us to give evidence of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating ability of P1 towards Fe3+. The pFe3+ value 22.0 of P1-iron complexes is noticeably higher than that of deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases. This is due on one side to the tautomeric change to the catechol form, and on the other to the lower protonation constant of the OH group. Bio-distribution studies on mice allowed us to confirm in vivo the efficacy of P1. Furthermore the coordinating ability toward Al3+, Cu2+ and Zn2+ has been studied to evaluate the possible use of P1 against a second toxic metal ion (Al3+), and to envisage its potential influence on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these ions, not higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron chelator.
- Lachowicz,Nurchi,Crisponi,Jaraquemada-Pelaez,Arca,Pintus,Santos,Quintanova,Gano,Szewczuk,Zoroddu,Peana,Domínguez-Martín,Choquesillo-Lazarte
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p. 6517 - 6528
(2016/05/09)
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- INHIBITORS OF DNA GYRASE FOR THE TREATMENT OF BACTERIAL INFECTIONS
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The present invention relates to compounds which specifically inhibit bacterial DNA Gyrase and can be used for the treatment of respiratory tract infections.
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- The design of efficient and selective routes to pyridyl analogues of 2,3-dihydro-1,4-benzodioxin-6-carbaldehyde
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This Letter describes the synthetic routes to challenging pyridyl analogues of 2,3-dihydro-1,4-benzodioxin- 6-carbaldehyde which were key intermediates for our antibacterial medicinal chemistry programme. All routes described started from kojic acid (8) and have been used to give multigram quantities of each aldehyde.
- Barfoot, Christopher W.,Brown, Pamela,Dabbs, Steven,Davies, David T.,Hennessy, Alan J.,Miles, Timothy J.,Pearson, Neil D.
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scheme or table
p. 5038 - 5040
(2011/01/04)
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- ANTIBACTERIAL AGENTS
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2H-chromen-2-one derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
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Page/Page column 33
(2008/06/13)
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- ANTIBACTERIAL AGENTS
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Naphthalene, quinoline, quinoxaline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
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Page/Page column 37
(2010/11/25)
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- ANTIBACTERIAL AGENTS
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Naphthyridine and quinoline derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
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Page/Page column 24
(2008/06/13)
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- ANTIBACTERIAL AGENTS
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Naphthyridine and related derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
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Page/Page column 24
(2008/06/13)
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- ANTIBACTERIAL AGENTS
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Naphthalene, quinoline, quinoxaline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.
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Page/Page column 36
(2010/10/20)
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- COMPOUNDS
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Piperidine derivatives and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly in man.
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Page/Page column 54
(2008/06/13)
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- Drug for ameliorating brain diseases
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The present invention discloses a drug for ameliorating brain diseases which comprises as an active ingredient a compound represented by the following formula (1): STR1 or a salt thereof. Because of inhibiting a decrease in brain neurons and promoting branching of neurites, this drug is efficacious in the prevention and treatment of dementia, etc. in association with degeneration and sloughing of brain neurons.
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