Entity

Time filter

Source Type


Chioua M.,Laboratorio Of Quimica Medica | Samadi A.,Laboratorio Of Quimica Medica | Soriano E.,SEPCO | Infantes L.,CSIC - Institute of Physical Chemistry "Rocasolano" | Marco-Contelles J.,Laboratorio Of Quimica Medica
Advanced Synthesis and Catalysis | Year: 2014

We report here that the silver triflate-catalyzed cyclization of 2-amino-6-propargylamineazines affords new and highly functionalized iminoimidazoazines. We have investigated the scope and limitations of the present methodology, and some aspects of the reactivity of the resulting iminoimidazopyridines have been explored, and a DFT-based mechanistic analysis of the silver triflate-catalyzed cyclization has been undertaken. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Chioua M.,Laboratorio Of Quimica Medica | Soriano E.,SEPCO | Infantes L.,CSIC - Institute of Physical Chemistry "Rocasolano" | Jimeno M.L.,CENQUIOR CSIC | And 2 more authors.
European Journal of Organic Chemistry | Year: 2013

We report herein the silver-catalyzed cycloisomerization of readily available N-(prop-2-yn-1-yl)pyridine-2-amines as a new and practical method for the synthesis of differently substituted 3-methylimidazo[1,2-a]pyridines. The isomerization reactions proceeded under mild reactions conditions to give good yields and excellent regioselectivity. A DFT-based mechanistic analysis is also reported. The silver-catalyzed cycloisomerization of readily available N-(prop-2-yn-1-ylamino)pyridines is a new and practical method for the synthesis of differently substituted 3-methylimidazo[1,2-a]pyridines, suitable intermediates for further synthetic transformations and modulation, that proceeds under mild reaction conditions to give good-to-high yields and excellent regioselectivity. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Bautista-Aguilera O.M.,Laboratorio Of Quimica Medica | Samadi A.,Laboratorio Of Quimica Medica | Chioua M.,Laboratorio Of Quimica Medica | Nikolic K.,University of Belgrade | And 10 more authors.
Journal of Medicinal Chemistry | Year: 2014

On the basis of N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine (II, ASS234) and QSAR predictions, in this work we have designed, synthesized, and evaluated a number of new indole derivatives from which we have identified N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine (2, MBA236) as a new cholinesterase and monoamine oxidase dual inhibitor. © 2014 American Chemical Society. Source


Chioua M.,Laboratorio Of Quimica Medica | Perez-Pena J.,Complutense University of Madrid | Garcia-Font N.,Complutense University of Madrid | Moraleda I.,University of Alcala | And 5 more authors.
Future Medicinal Chemistry | Year: 2015

Aim: Due to the complex nature of Alzheimer's disease, there is a renewed search for multipotent, nonhepatotoxic tacrines. Results: This paper describes the synthesis and in vitro biological evaluation of eight new racemic 3-methyl-4-aryl-2,4,6,7,8,9-hexahydropyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolin-5-amines (pyranopyrazolotacrines, PPT) as nonhepatotoxic multipotent tacrine analogs. Among these compounds, PPT4 is the less hepatotoxic in the cell viability assay on HepG2 cells, showing a good neuroprotective effect in the decreased cortical neuron viability induced by oligomycin A/rotenone analysis. PPT4 is a selective and good, noncompetitive EeAChE inhibitor, able to completely inhibit the Aβ1-40 aggregation induced by acetylcholinesterase. Conclusion: A new family of nonhepatotoxic showing selective acetylcholinesterase inhibition, permeable tacrine analogs have been discovered for the potential treatment of Alzheimer's disease. © 2015 Future Science Ltd. Source


Silva D.,University of Lisbon | Silva D.,Laboratorio Of Quimica Medica | Chioua M.,Laboratorio Of Quimica Medica | Samadi A.,Laboratorio Of Quimica Medica | And 12 more authors.
ACS Chemical Neuroscience | Year: 2013

The synthesis, molecular modeling, and pharmacological analysis of phenoxyalkylamino-4-phenylnicotinates (2-7), phenoxyalkoxybenzylidenemalononitriles (12, 13), pyridonepezils (14-18), and quinolinodonepezils (19-21) are described. Pyridonepezils 15-18 were found to be selective and moderately potent regarding the inhibition of hAChE, whereas quinolinodonepezils 19-21 were found to be poor inhibitors of hAChE. The most potent and selective hAChE inhibitor was ethyl 6-(4-(1-benzylpiperidin-4-yl) butylamino)-5-cyano-2-methyl-4-phenylnicotinate (18) [IC50 (hAChE) = 0.25 ± 0.02 μM]. Pyridonepezils 15-18 and quinolinodonepezils 20-21 are more potent selective inhibitors of EeAChE than hAChE. The most potent and selective EeAChE inhibitor was ethyl 6-(2-(1-benzylpiperidin-4-yl)ethylamino)-5- cyano-2-methyl-4-phenylnicotinate (16) [IC50 (EeAChE) = 0.0167 ± 0.0002 μM], which exhibits the same inhibitory potency as donepezil against hAChE. Compounds 2, 7, 13, 17, 18, 35, and 36 significantly prevented the decrease in cell viability caused by Aβ1-42. All compounds were effective in preventing the enhancement of AChE activity induced by Aβ1-42. Compounds 2-7 caused a significant reduction whereas pyridonepezils 17 and 18, and compound 16 also showed some activity. The pyrazolo[3,4-b]quinolines 36 and 38 also prevented the upregulation of AChE induced by Aβ1-42. Compounds 2, 7, 12, 13, 17, 18, and 36 may act as antagonists of voltage sensitive calcium channels, since they significantly prevented the Ca2+ influx evoked by KCl depolarization. Docking studies show that compounds 16 and 18 adopted different orientations and conformations inside the active-site gorges of hAChE and hBuChE. The structural and energetic features of the 16-AChE and 18-AChE complexes compared to the 16-BuChE and 18-BuChE complexes account for a higher affinity of the ligand toward AChE. The present data indicate that compounds 2, 7, 17, 18, and 36 may represent attractive multipotent molecules for the potential treatment of Alzheimer's disease. © 2013 American Chemical Society. Source

Discover hidden collaborations