Potential latent nitrogen mustard derivatives designed to target monoamine oxidase rich cells

Bioorg Med Chem. 1997 Jul;5(7):1321-5. doi: 10.1016/s0968-0896(97)00056-4.

Abstract

The monoamine oxidases A and B (MAO-A and MAO-B) catalyze the alpha-carbon oxidation of a variety of 4-substituted 1-methyl-1,2,3,6-tetrahydropyridine derivatives to yield the corresponding 2,3-dihydropyridinium species. When the substituent at C-4 of the tetrahydropyridine moiety is a carbamoyloxy functionality, the resulting dihydropyridinium metabolite undergoes spontaneous hydrolytic cleavage to yield 1-methyl-5,6-dihydro-4-pyridone, CO2, and the corresponding secondary amine. In this paper we summarize our efforts to exploit this metabolic pathway to develop latent nitrogen mustard derivatives related to the oxazaphosphorine antitumor agent cyclophosphamide which may target MAO-A and/or MAO-B rich cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cattle
  • Humans
  • Kinetics
  • Monoamine Oxidase / metabolism*
  • Nitrogen Mustard Compounds / chemical synthesis*
  • Nitrogen Mustard Compounds / metabolism
  • Nitrogen Mustard Compounds / pharmacology*
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Antineoplastic Agents
  • Nitrogen Mustard Compounds
  • Monoamine Oxidase