- Click chemistry synthesis, biological evaluation and docking study of some novel 2′-hydroxychalcone-triazole hybrids as potent anti-inflammatory agents
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A hybrid pharmacophore approach is used to design and synthesize two novel series of 2′-hydroxychalcone-triazole hybrid molecules 6a-j and 8a-j. These compounds were fully characterized by spectral and elemental analyses. They were evaluated in vitro and in vivo for anti-inflammatory activity. Most of compounds were selective inhibitors for COX-2. Among them, compounds 6d, 6f, 6i, 8c, 8e and 8h demonstrated highly potent dual inhibition of COX-2 (IC50 = 0.037–0.041 μM) and 15-LOX (IC50 = 1.41–1.80 μM). Compounds 6i, 8c and 8h showed 116%, 113% and 109% of the in vivo anti-inflammatory activity of celecoxib. Therefore, compounds 6d, 6f, 6i, 8c, 8e and 8h-j are potent dual inhibitors of COX-2 and 15-LOX. Docking study over COX-2 and 15-LOX active sites ensures the binding affinity and selectivity. These compounds are promising candidates for further development as anti-inflammatory drugs.
- Abdu-Allah, Hajjaj H. M.,Boshra, Andrew N.,Hayallah, Alaa M.,Mohammed, Anber F.
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- Identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives as potassium channel activators and anti-inflammatory agents
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The present study described the design, synthesis and identification of 3-hydroxy-4[3,4-dihydro-3-oxo-2H-1,4-benzoxazin-4-yl]-2,2-dimethyldihydro-2H-benzopyran derivatives. Their biological activity was tested for KATP channel opener as antihypertensives, COX-1 and COX-2 activity. The results were compared with the activity of cromakalim, ibuprofen and celecoxib. The study aimed at exploring the influence of introduction of a benzoxazine substituent at position 6 of various derivatives of benzopyrans in order to improve biological activity. Several compounds were found to be equipotent or even more potent than cromakalim. Out of these nitro-substituted benzopyrans, nitro substitution at benzoxazino group possessed potent antihypertensive activity in the R/S isomers. With amino derivatives, activity remains constant when compared with standard cromakalim. Similarly, compounds 17b, 17c, 17e and 17h have exhibited around 40 % inhibition of COX-1 as compared to the inhibition of COX-2. Only two compounds 17g and 17i exhibited effective inhibition more than 50 % of COX-2 compared with the inhibition of COX-1 at a concentration of 0.3 mg/ml.
- Bano, Mohsina,Barot, Kuldipsinh P.,Jain, Shailesh V.,Ghate, Manjunath D.
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p. 3008 - 3020
(2015/03/18)
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- N-sulfamoyl-N'-benzopyranpiperidine compounds and uses thereof
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N-sulfamoyl-N′-benzopyranpiperidine compounds of formula I and their physiologically acceptable acid addition salts, pharmaceutical compositions comprising them, processes for their preparation, and their use for the treatment and/or inhibition of glaucoma, epilepsy, bipolar disorders, migraine, neuropathic pain, obesity, type II diabetes, metabolic syndrome, alcohol dependence, and/or cancer, and related concomitant and/or secondary diseases or conditions.
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Page/Page column 8
(2008/06/13)
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- N-SULFAMOYL-N’-BENZOPYRANPIPERIDINES AS INHBITORS OF CARBONIC ANHYDRASES
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The present invention relates to novel N-sulfamoyl-N'-benzopyranpiperidines of general formula (I) and their physiologically acceptable acid addition salts, to pharmaceutical compositions comprising them, processes for their preparation, and their use for the prophylaxis and/or treatment and/or prevention and/or inhibition of glaucoma, epilepsy, bipolar disorders, migraine, neuropathic pain, obesity, type II diabetes, metabolic syndrome, alcohol dependence, and/or cancer, and its concomitant and/or secondary diseases or conditions.
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Page/Page column 16
(2008/06/13)
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- Potential therapeutic antioxidants that combine the radical scavenging ability of myricetin and the lipophilic chain of vitamin E to effectively inhibit microsomal lipid peroxidation
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The flavonol myricetin, reacts with oxygen-centred galvinoxyl radicals 28 times faster than d-α-tocopherol (vitamin E), the main lipid-soluble antioxidant in biological membranes. Moreover, each myricetin molecule reduces twice as many such radicals as vitamin E. However, myricetin fails to protect vitamin E-deficient microsomes from lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances (TBARS). Novel and potentially therapeutic antioxidants have been prepared that combine the radical-scavenging ability of a myricetin-like head group with a lipophilic chain similar to that of vitamin E. C6-C12 alkyl chains are attached to the A-ring of either a 3,3′,4 ′,5′-tetrahydroxyflavone or a 3,2 ′,4′,5′-tetrahydroxyflavone head group to give lipophilic flavonoids (ClogP=4 to 10) that markedly inhibit iron-ADP catalysed oxidation of microsomal preparations. Orientation of the head group as well as total lipophilicity are important determinants of antioxidant efficacy. MM2 models indicate that our best straight chain 7-alkylflavonoids embed to the same depth in the membrane as vitamin E. The flavonoid head groups are prepared by aldol condensation followed by Algar-Flynn-Oyamada (AFO) oxidation or by Baker-Venkataraman rearrangement. The alkyl tails are introduced by Suzuki or Negishi palladium-catalysed cross-coupling or by cross-metathesis catalysed by first generation Grubbs catalyst, which tolerate phenolic hydroxyl and ketone groups.
- Bennett, Christopher J.,Caldwell, Stuart T.,McPhail, Donald B.,Morrice, Philip C.,Duthie, Garry G.,Hartley, Richard C.
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p. 2079 - 2098
(2007/10/03)
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- FLAVONOID COMPOUNDS AS THERAPEUTIC ANTIOXIDANTS
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Novel flavonoid compounds having anti-oxidant activity are described. The compounds have been shown to exhibit anti-oxidative properties in biological systems and their utility in a sunscreen or skincare composition or to treat conditions involving oxidative damage, especially curative or prophylactic treatment of Alzheimer's disease or ischaemia-reperfusion injury, is described.
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- Synthesis and Biochemical Evaluation of a Series of Aminoflavones as Potential Inhibitors of Protein-Tyrosine Kinases p56lek, EGFr, and p60v-src
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A series of nitroflavones, 8a-p, and their corresponding aminoflavone hydrochloride salts, 10a-p, was synthesized.The preparation of nitroflavones 8b-i,o,p began with commercially available o-hydroxyacetophenones 2b-f which were converted to o-hydroxynitroacetophenones 3a-h via a variety of nitration methods, followed by condensation with nitrobenzyl chlorides and cyclization under acidic condition.The nitroflavones 8a,j-n were prepared by nitration of the corresponding flavones 7a-e.These new compounds were evaluated for their abilities to inhibit the in vitro protein-tyrosine kinase activities of p56lek, EGFr, and p60v-src, and all of the active compounds were amino-substituted flavones.None of the nitroflavones inhibited the enzymes.The most active substance in this series against p56lek was compound 10j, which had an IC50 of 18 μM.When tested versus EGFr, compounds 10a,m displayed IC50's of 8.7 and 7.8 μM, respectively.Against p60v-src, 10a,m showed IC50 values of 28.8 and 38.4 μM, respectively.
- Cushman, Mark,Zhu, Helen,Geahlen, Robert L.,Kraker, Alan J.
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p. 3353 - 3362
(2007/10/02)
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- Synthesis and structure-activity relationships of new β-adrenoreceptor antagonists. Evidence for the electrostatic requirements for β-adrenoreceptor antagonists
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A series of mono- and disubstituted phenoxypropanolamines, structurally related to practolol and acebutolol, has been synthesized and tested for β-adrenoreceptor blocking activity. Structure-activity relationships are discussed. The reasons for the lack of activity of compounds 3n and 4n have also been examined. The results suggest that the negative electrostatic potential above the phenyl ring of phenoxypropanolamines is essential for binding activity and point to the presence of an electropositive residue in the β-adrenoreceptor binding site.
- Kettmann,Csollei,Racanska,Svec
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p. 843 - 851
(2007/10/02)
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