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Bioorg Med Chem ; 110: 117829, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39002183

RESUMO

In pharmaceutical science and drug design the versatility of the pyrrolidine scaffold relating to spatial arrangement, synthetic accessibility and pharmacological profile is a largely explored and most likely interesting one. Nonetheless, few evidences suggest the pivotal role of pyrrolidine as scaffold for multipotent agents in neurodegenerative diseases. We then challenged the enrolling in the field of Alzheimer disease of so far not ravelled targets of this chemical cliché with a structure based and computer-aided design strategy focusing on multi-target action, versatile synthesis as well as pharmacological safeness. To achieve these hits, ten enantiomeric pairs of compounds were obtained and tested, and the biological data will be here presented and discussed. Among the novel compounds, coumarin and sesamol scaffolds containing analogues resulted promising perspectives.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Pirrolidinas , Pirrolidinas/química , Pirrolidinas/síntese química , Pirrolidinas/farmacologia , Humanos , Doença de Alzheimer/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Estereoisomerismo , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/síntese química , Animais , Relação Estrutura-Atividade
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