MAO inhibitors and their wider applications: a patent review

ABSTRACT

Introduction: Monoamine oxidase (MAO) inhibitors, after the initial ‘golden age’, are currently used as third-line antidepressants (selective MAO-A inhibitors) or clinically enrolled as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). However, the research within this field is always increasing due to their pivotal role in modulating synaptic functions and monoamines metabolism.

Areas covered: In this paper, MAO inhibitors (2015–2017) are disclosed ordering all the patents according to their chemical scaffold. Structure-activity relationships (SARs) are extrapolated for the most investigated chemotypes (coumarins, pyrazole/oxazepinones, (hetero)arylamides). 108 Compounds are divided into two main groups: newly synthesized molecules and naturally-occurring metabolites. Finally, new therapeutic options are outlined to ensure a more complete view on the potential of these inhibitors.

Expert opinion: New proposed MAO inhibitors are endowed with a marked isoform selectivity, with innovative therapeutic potential toward other targets (gliomas, inflammation, muscle dystrophies, migraine, chronic pain, pseudobulbar affect), and with a promising ability to address multi-faceted pathologies such as Alzheimer’s disease. The increasing number of patents is analyzed collecting data from 2002 to 2017.

KEYWORDS:

• Alzheimer’s disease
• depression
• multi-target inhibitors
• monoamine oxidase
• natural products
• Parkinson’s disease

Article highlights

• 108 synthetic molecules and naturally-occurring metabolites were licensed as MAO inhibitors

• Coumarin derivatives were the most studied compounds in order to obtain selective MAO-B inhibitors

• Coumarin/tacrine hybrids were endowed with promising dual MAO/ChE inhibition

• Drug repurposing of old MAO inhibitors was proposed for alternative therapeutic options

• The discovery of natural MAO-A inhibitors could avoid the risk of drug-food interaction

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.