Benzoxazoles as Selective Monoamine Oxidase B (MAO‐B) Inhibitors

Abstract

Parkinson's disease (PD) is a central nervous system disorder accompanied by tremor, slow movement, motor impairment, and dementia. 1,2 These symptoms of PD mainly result from the death of dopaminergic neurons in substantia nigra (SN) and the deficiency of dopamine inside the brain. 3 Dopamine is a type of monoamine neurotransmitter and acts as a chemical messenger to regulate neuronal signaling in brain, thereby controls motor functions. 4 Levodopa (L-dopa) is the major treatment for PD and exerts its effect as a dopamine precursor. 5 However, doparesistance or serious complications are observed after an initial period of treatment. 6 Besides L-dopa treatment, another therapeutic way to restore dopamine function is the suppression of dopamine catabolism. Monoamine oxidase (MAO) is involved in down-regulation of dopamine level which catalyzes the deamination and degradation of dopamine. 7 Inhibition of MAO blocks the breakdown of dopamine, thereby prolongs the action of dopamine in the brain. 8 There are two isoforms of MAO-A and MAO-B. Although they share about 70% of structure similarity, MAO-A and -B exhibit different substrate specificity as well as diverse regional distribution in brain tissue. 9 MAO-B has been regarded as a therapeutic target for PD in clinic because the elevated activity of MAO-B was observed in the SN of PD patients. 10