Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B

J Med Chem. 2003 Mar 13;46(6):917-20. doi: 10.1021/jm0256124.

Abstract

N-Benzyl- and N-propargyl-1H-pyrrole-2-carboxyamides and some related methylenamines were synthesized and tested for their monoamine oxidase types A and B inhibitory activity. 2-(N-Methyl-N-propargylaminomethyl)-1H-pyrrole (24) was the most potent MAO-A inhibitor of the series [K(i)(MAO-A) = 0.0054 microM], but it was not selective. Inhibitors N-4-fluorobenzyl-1H-pyrrole-2-carboxamide (12) and N-cyclohexylmethyl-1H-pyrrole-2-carboxamide (25) showed the highest MAO-A selectivity indexes (SI) corresponding to 2025 and >2500, respectively, while 2-(N-methyl-N-benzylaminomethyl)-1H-pyrrole (21) was the most selective MAO-B inhibitor, having an SI of 0.0057.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemical synthesis*
  • Alkynes / chemistry
  • Alkynes / pharmacology
  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology
  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology
  • Animals
  • Brain / enzymology
  • Brain / ultrastructure
  • Cattle
  • Isoenzymes / metabolism
  • Mitochondria / enzymology
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Structure-Activity Relationship

Substances

  • Alkynes
  • Amides
  • Amines
  • Isoenzymes
  • Monoamine Oxidase Inhibitors
  • Pyrroles
  • Monoamine Oxidase