Arzneimittelforschung 2012; 62(11): 513-518
DOI: 10.1055/s-0032-1323662
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

The Inhibition of Monoamine Oxidase by 8-(2-Phenoxyethoxy)Caffeine Analogues

B. Strydom
1   Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa
J. J. Bergh
1   Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa
J. P. Petzer
1   Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa
› Author Affiliations
Further Information

Publication History

received 11 May 2012

accepted 24 July 2012

Publication Date:
31 August 2012 (online)


Previous studies have documented that substituted 8-oxycaffeines act as inhibitors of human monoamine oxidase (MAO) B. A particularly potent inhibitor among the reported compounds was 8-(2-phenoxyethoxy)caffeine with an IC50 value of 0.383 µM towards MAO-B. In an attempt to improve on the inhibition potency of this compound and to discover highly potent reversible MAO-B inhibitors, in the present study, a series of 8-(2-phenoxyethoxy)caffeine analogues containing various substituents on C4 of the phenoxy ring, were synthesized and evaluated as inhibitors of human MAO-A and -B. The results show that the 8-(2-phenoxyethoxy)caffeine analogues are selective and reversible MAO-B inhibitors with the most potent homologue, 8-{2-[4-(trifluoromethyl)phenoxy]ethoxy}caffeine, exhibiting an IC50 value of 0.061 μM. These highly potent inhibitors are useful leads in the design of therapies for neurodegenerative disorders such as Parkinson’s disease.

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