Browsing by Author "Carreiras, MC"
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- 1,6-C-H and 1,5-O-Si insertion reactions of alkylidenecarbene derivatives of monosaccharidesPublication . Van Nhien, AN; Leon, R; Postel, D; Carreiras, MC; Garcia, AG; Marco-Contelles, JA new protocol has been developed for the generation of alkylidenecarbene derivatives of monosaccharides based on the reaction of trimethylsilylazide and Bu2SnO with alpha-cyanomesylates derived from uloses. When this method is applied to conveniently functionalized carbohydrate derivatives it provides novel heterocyclic ring systems by the rare 1,6-C-H or 1,5-O-Si insertion reactions.
- Acetylcholinesterase Inhibitory Activity of Oxazole DerivativesPublication . Dias, C; Brito, MA; Eleutério, A; Marco, JL; Brites, D; Carreiras, MC
- Electron Ionization Mass Spectrometric Study of Some Substituted 1,3-oxazolesPublication . Salgueiro, P; Dias, C; Carreiras, MC; Borges, C
- Medicinal ChemistryPublication . Moreira, R; Carreiras, MC; Lopes, F; Rocha, MJP; Mendes, E; LConstantino, Dias,; Santos, MM; Lavrado, J; Capela, R; Santana, AB; Valente, E; Rodrigues, T
- Recent approaches to novel anti-Alzheimer therapyPublication . Carreiras, MC; Marco, JLInsufficient cholinergic neurotransmission in AD is responsible for a progressive loss of cognition and motor capacities. The cholinergic hypothesis has provided the rationale for the current treatment approaches based on acetylcholinesterase inhibitors. However, recent data focus on the complex nature of AD and disclose the involvement of other neurotransmitters such as serotonin, noradrenalin, dopamine, histamine, excitatory amino acids and neuropeptides among others. Interestingly, recent research has revealed that in severe AD brains the levels of AChE are considerably reduced whereas BuChE activity increases, thus aggravating the toxicity of betaA. In such instances, it is possible that BuChE may be a more suitable target than AChE. Oxidative stress has been implicated in CNS degenerative disorders such as AD and PD. Therefore, owing to their capacity to inhibit oxidative damage, MAOIs are potential candidates as anti-Alzheimer drugs. More recently, a novel drug - TV3326 - was designed, based upon two pharmacophores: the carbamate moiety from rivastigmine, an AChE inhibitor; and the propargyl group from rasagiline, a MAO inhibitor. This drug exhibits cholinesterase and selective brain MAO inhibitory activities, reduces apoptosis and stimulates the processing of APPalpha, hence reducing the possibility of generation of the toxic betaA. Thus, TV3326 may be expected to contribute positively to the cognitive benefits of Alzheimer's patients. Anyhow, the development of drugs with several targets and diverse pharmacological properties may conclusively demonstrate the most beneficial therapy.
- Synthesis and acetylcholinesterase/butyrylcholin-esterase inhibition activity of 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro(and thieno)[2,3-b]quinolines, and 4-amino-5,6,7,8,9-pentahydro-2,3-diphenylcyclohepta[e]furo(and thieno)-[2,3-b]pyridinePublication . Marco, JL; de los Rios, C; Carreiras, MC; Banos, JE; Badia, A; Vivas, NMThe acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activities of a series of 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (10-12)/4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (14) and 4-amino-5,6,7,8,9-pentahydro-2,3-diphenylcyclohepta[e]furo[2,3-b]pyridine (13)/4amino-5,6,7,8,9-pentahydro-2,3-phenylcyclohepta[e]thieno[2,3-b]pyridine (15) are described. These compounds are tacrine (THA) analogues which have been prepared either from readily available 2-amino-3-cyano-4,5-diarylfurans (16-18) or from 2-amino-3-cyano-4,5-diphenylthiophene (19), via Friedlander condensation with cyclohexanone or cycloheptanone. These compounds are competitive inhibitors for acetylcholinesterase, the more potent being compound (13) which is threefold less active than tacrine. The butyrylcholinesterase inhibition activity is significant only in compounds 10 and 13, which are ten-fold less active than tacrine. It is found that the products 11 and 12 strongly inhibit acetylcholinesterase, and show excellent selectivity regarding butyrylcholinesterase.
- Synthesis and acetylcholinesterase/butyrylcholinesterase inhibition activity of new tacrine-like analoguesPublication . Marco, JL; de los Rios, C; Carreiras, MC; Banos, JE; Badia, A; Vivas, NMThe synthesis and preliminary results for acetylcholinesterase and butyrylcholinesterase inhibition activity of a series of pyrano[2,3-b]quinolines (2, 3) and benzonaphthyridines (5, 6) derivatives are described. These molecules are tacrine-like analogues which have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyrans and 6-amino-5-cyanopyridine s]-3-carboxylates via Friedlander condensation with selected ketone s. These compounds showed moderate acetylcholinesterase inhibition activity, the more potent (2e, 5b) being 6 times less active than tacrine. The butyrylcholinesterase activity of some of these molecules is also discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.
- Synthesis and Biological Assessment of Furoquinolines, Pyrroloquinolines and Analogues Towards Cholinesterases and Monoamine Oxidases A and BPublication . Martins, C; Carreiras, MC; Mendes, E; de los Rios, C; Léon, R; Ramsay, R; Marco-Contelles, J
- Synthesis, biological evaluation and molecular modelling of diversely functionalized heterocyclic derivatives as inhibitors of acetylcholinesterase/butyrylcholinesterase and modulators of Ca2+ channels and nicotinic receptorsPublication . Marco, JL; de los Rios, C; Garcia, AG; Villarroya, M; Carreiras, MC; Martins, C; Eleuterio, A; Morreale, A; Orozco, M; Luque, FJThe synthesis and the biological activity of compounds 5-40 as inhibitors of acetyleholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as modulators of voltage-dependent Ca2+ channels and nicotinic receptors, are described. These molecules are tacrine analogues, which have been prepared from polyfunctionalized 6-amino-5-cyano-4H-pyrans, 6-amino-5-cyano-pyridines and 5-amino-2-aryl-3-cyano-1,3-oxazoles via Friedlander reaction with selected cycloalkanones. These compounds are moderate acetylcholinesterase and butyrylcholinesterase inhibitors, the BuChE/AChE selectivity of the most active molecules ranges from 10.0 (compound 29) to 76.9 (compound 16). Interestingly, the 'oxazolo-tacrine' derivatives are devoid of any activity. All compounds showed an important inhibitory effect on the nicotinic acetylcholine receptor. Most of them also blocked L-type Ca2+ channels, and three of them, 64, 19 and 67, the non-L type of Ca2+ channels. Molecular modelling studies suggest that these compounds might bind at the peripheral binding site of AChE, which opens the possibility to design inhibitors able to bind at both, the catalytic and peripheral binding sites of the enzyme. (C) 2004 Elsevier Ltd. All rights reserved.