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Title: | Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors | Authors: | Brandão, Pedro López, Óscar Leitzbach, Luisa Stark, Holger Fernández-Bolaños, José G. Burke, Anthony J. Pineiro, Marta |
Issue Date: | 11-Nov-2021 | Publisher: | ACS American Chemical Society | Project: | P. Brandão acknowledges FCT for the PhD grant PD/BD/ 128490/2017-CATSUS FCT-PhD Program. Coimbra Chemistry Centre (CQC) is supported by the Portuguese Agency for Scientific Research, “Fundação para a Ciência e a Tecnologia” (FCT) through project UIDB/00313/2020 and UIDP/00313/ 2020, cofunded by COMPETE2020-UE. We also acknowledge the UC-NMR facility for obtaining the NMR data (www. nmrccc.uc.pt). This work was also financed by the FEDER Funds through the Operational Competitiveness Factors ProgramCOMPETEand by National Funds through FCTFoundation for Science and Technologywithin the scope of the project UIDB/50006/2020. Ó. López would also like to thank the Dirección General de Investigación of Spain (CTQ2016-78703-P), Junta de Andalucía (FQM134), and FEDER (501100008530) for financial support. Partial support from the EU COST Actions CA15135 (to HS and AJB), CA18133 (to HS), and CA18240 (to HS) is also acknowledged. | Serial title, monograph or event: | ACS Medicinal Chemistry Letters | Volume: | 12 | Issue: | 11 | Abstract: | Molecular hybridization is a valuable approach in drug discovery. Combining it with multicomponent reactions is highly desirable, since structurally diverse libraries can be attained efficiently in an eco-friendly manner. In this work, isatin is used as the key building block for the Ugi 4-center 3-component reaction synthesis of oxindole-lactam hybrids, under catalyst-free conditions. The resulting oxindole-β-lactam and oxindole-γ-lactam hybrids were evaluated for their potential to inhibit relevant central nervous system targets, namely cholinesterases and monoamine oxidases. Druglikeness evaluation was also performed, and compounds 4eca and 5dab exhibited great potential as selective butyrylcholinesterase inhibitors, at the low micromolar range, with an interesting predictive pharmacokinetic profile. Our findings herein reported suggest oxindole-lactam hybrids as new potential agents for the treatment of Alzheimer's disease. | URI: | https://hdl.handle.net/10316/107441 | ISSN: | 1948-5875 | DOI: | 10.1021/acsmedchemlett.1c00344 | Rights: | embargoedAccess |
Appears in Collections: | I&D CQC - Artigos em Revistas Internacionais |
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Brandao2021ACSMedChemLett.pdf | 2.89 MB | Adobe PDF | View/Open |
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