Design of novel nicotinamides as potent and selective monoamine oxidase a inhibitors

  • Bioorg Med Chem. 2010 Feb 15;18(4):1659-64. doi: 10.1016/j.bmc.2009.12.065.
Lei Shi  1 ,  Ying Yang ,  Zi-Lin Li ,  Zhen-Wei Zhu ,  Chang-Hong Liu ,  Hai-Liang Zhu
Affiliations
  • 1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
PMID: 20117937 DOI: 10.1016/j.bmc.2009.12.065
Abstract

A series of N-(2-morpholinoethyl)nicotinamide (1-13) and N-(3-morpholinopropyl)nicotinamide derivatives (14-26) have been designed, synthesized and evaluated in vitro for their Monoamine Oxidase (MAO) A and B inhibitory activity and selectivity. Most of these synthesized compounds proved to be potent, and selective inhibitors of MAO-A rather than of MAO-B. 5-Chloro-6-hydroxy-N-(2-morpholinoethyl)nicotinamide (13) displayed the highest MAO-A inhibitory potency (IC(50)=0.045 microM) and a good selectivity. 2-Bromo-N-(2-morpholinoethyl)nicotinamide (3) was the most potent MAO-B Inhibitor with the IC(50) value of 0.32 microM, but it was not selective. Molecular dockings of compound 13 were performed in order to give structural insights regarding the MAO-A selectivity.

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