Synthesis and anticonvulsant activity of phenoxyacetyl derivatives of amines, including aminoalkanols and amino acids

A series of 17 new phenoxyacetamides has been prepared multistep chemical synthesis as a continuation of the research carried out by our group on di- and tri-substituted phenoxyalkyl and phenoxyacetyl derivatives of amines. The obtained compounds vary in an amide component, for example aminoalkanol...

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Published inMedChemComm Vol. 9; no. 11; pp. 1933 - 1948
Main Authors Pańczyk, Katarzyna, Żelaszczyk, Dorota, Koczurkiewicz, Paulina, Słoczyńska, Karolina, Pękala, Elżbieta, Żesławska, Ewa, Nitek, Wojciech, Żmudzki, Paweł, Marona, Henryk, Waszkielewicz, Anna
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 01.11.2018
Subjects
Amines
Amino acids
Animal models
Anticonvulsants
Astrocytes
Cell proliferation
Chemical synthesis
Crystallography
Cytotoxicity
Derivatives
Hippocampus
Kindling
Mutagenicity
Neurotoxicity
Organic chemistry
Rats
Rodents
Stability analysis
Toxicity
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Summary:A series of 17 new phenoxyacetamides has been prepared multistep chemical synthesis as a continuation of the research carried out by our group on di- and tri-substituted phenoxyalkyl and phenoxyacetyl derivatives of amines. The obtained compounds vary in an amide component, for example aminoalkanol or (un)modified amino acid moieties were introduced. The structures of selected products were confirmed by means of crystallographic methods. All 17 compounds were the subject of preliminary screening for potential anticonvulsant activity (MES, 6 Hz and/or scMET tests) and neurotoxicity (rotarod) in mice after intraperitoneal administration, while several active compounds were subsequently examined in additional models ( MES and rotarod - rats, or , hippocampal kindling - rats, ). Finally, safety studies (cytotoxicity and cell proliferation assays on astrocytes, metabolic stability assessment, mutagenicity evaluation) were performed for several active compounds, including the most promising one ( -(-)-2-(2,6-dimethylphenoxy)- -(1-hydroxypropan-2-yl)acetamide, MES ED = 12.00 mg per kg b.w., rats, ).
ISSN:2040-2503
2040-2511
DOI:10.1039/c8md00430g