4553-21-3Relevant articles and documents
Novel donepezil?arylsulfonamide hybrids as multitarget-directed ligands for potential treatment of Alzheimer?s disease
Queda, Fausto,Calò, Sonia,Gwizdala, Karolina,Magalh?es, Jo?o D.,Cardoso, Sandra M.,Chaves, Sílvia,Piemontese, Luca,Amélia Santos
, (2021/04/26)
Alzheimer’s disease (AD) is one of the most devastating neurodegenerative disorders, characterized by multiple pathological features. Therefore, multi-target drug discovery has been one of the most active fields searching for new effective anti-AD therapies. Herein, a series of hybrid compounds are reported which were designed and developed by combining an aryl-sulfonamide function with a benzyl-piperidine moiety, the pharmacophore of donepezil (a current anti-AD acetylcholinesterase AChE inhibitor drug) or its benzyl-piperazine analogue. The in vitro results indicate that some of these hybrids achieve optimized activity towards two main AD targets, by displaying excellent AChE inhibitory potencies, as well as the capability to prevent amyloid-β (Aβ) aggregation. Some of these hybrids also prevented Aβ-induced cell toxicity. Significantly, drug-like properties were predicted, including for blood-brain permeability. Compound 9 emerged as a promising multi-target lead compound (AChE inhibition (IC50 1.6 μM); Aβ aggregation inhibition 60.7%). Overall, this family of hybrids is worthy of further exploration, due to the wide biological activity of sulfonamides.
Propionamide Derivatives as Dual μ-Opioid Receptor Agonists and σ1Receptor Antagonists for the Treatment of Pain
García, Mónica,Llorente, Virginia,Garriga, Lourdes,Christmann, Ute,Rodríguez-Escrich, Sergi,Virgili, Marina,Fernández, Bego?a,Bordas, Magda,Ayet, Eva,Burgue?o, Javier,Pujol, Marta,Dordal, Albert,Portillo-Salido, Enrique,Gris, Georgia,Vela, José Miguel,Almansa, Carmen
, p. 10139 - 10154 (2021/07/28)
A new series of propionamide derivatives was developed as dual μ-opioid receptor agonists and σ1receptor antagonists. Modification of a high-throughput screening hit originated a series of piperazinylcycloalkylmethyl propionamides, which were e
Piperazine-and piperidine-containing thiazolo[5,4-d]pyrimidine derivatives as new potent and selective adenosine a2a receptor inverse agonists
Varano, Flavia,Catarzi, Daniela,Vigiani, Erica,Vincenzi, Fabrizio,Pasquini, Silvia,Varani, Katia,Colotta, Vittoria
, p. 1 - 19 (2020/07/31)
The therapeutic use of A2A adenosine receptor (AR) antagonists for the treatment of neurodegenerative disorders, such as Parkinson and Alzheimer diseases, is a very promising approach. Moreover, the potential therapeutic role of A2A AR antagonists to avoid both immunoescaping of tumor cells and tumor development is well documented. Herein, we report on the synthesis and biological evaluation of a new set of piperazine-and piperidine-containing 7-amino-2-(furan-2-yl)thiazolo[5,4-d]pyrimidine derivatives designed as human A2A AR antagonists/inverse agonists. Binding and potency data indicated that a good number of potent and selective hA2A AR inverse agonists were found. Amongst them, the 2-(furan-2-yl)-N5-(2-(4-phenylpiperazin-1-yl)ethyl)thiazolo[5,4-d]pyrimidine-5,7-diamine 11 exhibited the highest A2A AR binding affinity (Ki = 8.62 nM) as well as inverse agonist potency (IC50 = 7.42 nM). In addition, bioinformatics prediction using the web tool SwissADME revealed that 8, 11, and 19 possessed good drug-likeness profiles.
