Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease

Title
Oxazolopyridines and thiazolopyridines as monoamine oxidase B inhibitors for the treatment of Parkinson’s disease
Authors
박혜리김지윤김태근조선미염미영문봉진추일한이재익임은정박기덕민선준남길수금교창이창준추현아
Keywords
MAOB inhibitor; Parkinson's Disease; Monoamine oxidase B; MAO-B; Oxazolopyridine; Thiazolopyridine
Issue Date
2013-09
Publisher
Bioorganic & medicinal chemistry
Citation
VOL 21, NO 17, 5480-5487
Abstract
In Parkinson’s disease, the motor impairments are mainly caused by the death of dopaminergic neurons. Among the enzymes which are involved in the biosynthesis and catabolism of dopamine, monoamine oxidase B (MAO-B) has been a therapeutic target of Parkinson’s disease. However, due to the undesirable adverse effects, development of alternative MAO-B inhibitors with greater optimal therapeutic potential towards Parkinson’s disease is urgently required. In this study, we designed and synthesized the oxazolopyridine and thiazolopyridine derivatives, and biologically evaluated their inhibitory activities against MAO-B. Structure–activity relationship study revealed that the piperidino group was the best choice for the R1 amino substituent to the oxazolopyridine core structure and the activities of the oxazolopyridines with various phenyl rings were between 267.1 and 889.5 nM in IC50 values. Interestingly, by replacement of the core structure from oxazolopyrine to thiazolopyridine, the activities were significantly improved and the compound 1n with the thiazolopyridine core structure showed the most potent activity with the IC50 value of 26.5 nM. Molecular docking study showed that van der Waals interaction in the human MAO-B active site could explain the enhanced inhibitory activities of thiazolopyridine derivatives.
URI
http://pubs.kist.re.kr/handle/201004/45233
ISSN
09680896
Appears in Collections:
KIST Publication > Article
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