Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of A beta-peptide aggregation inhibitors

• A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on A beta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer A beta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric A beta-peptide.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Other Basic Medicine (hsv//eng)

Nyckelord

RING-FUSED 2-PYRIDINONES

ALZHEIMERS-DISEASE

ELECTRON-TRANSFER

OLIGOMERS

ACIDS

NEUROTOXICITY

DERIVATIVES

MECHANISM

RADICALS

ESTERS

Chemistry

Kemi

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