58273-00-0Relevant academic research and scientific papers
Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky chemistry
Cagide,Silva,Reis,Gaspar,Borges,Gomes,Low
, p. 2832 - 2835 (2015)
The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of poten
Synthesis and evaluation of chromone derivatives as inhibitors of monoamine oxidase
Mpitimpiti, Annah N.,Petzer, Jacobus P.,Petzer, Anél,Jordaan, Johannes H. L.,Lourens, Anna C. U.
, p. 897 - 913 (2019/01/29)
Abstract: Based on reports that chromone compounds are good potency inhibitors of monoamine oxidase (MAO), the present study evaluates the effect of substitution with flexible side chains on the 3 position on MAO inhibition potency. Fifteen chromone derivatives were synthesised by reacting aromatic and aliphatic amines and alcohols with chromone 3-carboxylic acid in the presence of carbonyldiimidazole (CDI). This yielded chromane-2,4-dione and ester chromone derivatives. Generally, the esters exhibited weak MAO inhibition, while the chromane-2,4-dione derivatives showed promise as selective MAO-B inhibitors with IC50 values in the micromolar range. Compound 14b, 3-[(benzylamino)methylidene]-3,4-dihydro-2H-1-benzopyran-2,4-dione, was the most potent MAO-B inhibitor with an IC50 value of 638?μM. This compound was shown to be a reversible and competitive MAO-B inhibitor with a Ki of 94?μM. In conclusion, the effect of chain elongation and introduction of flexible substituents on position 3 of chromone were explored and the results showed that aminomethylidene substitution is preferable over ester substitution. Good potency MAO-B inhibitors may act as leads for the design and development of therapy for Parkinson’s disease where these agents reduce the central metabolism of dopamine. Graphical abstract: [Figure not available: see fulltext.].
