Synthesis and evaluation of new oxamniquine derivatives

Int J Pharm. 2002 Feb 21;233(1-2):35-41. doi: 10.1016/s0378-5173(01)00917-6.

Abstract

Oxamniquine derivatives were synthesized and evaluated as novel schistosomicide agents. Oxamniquine (1,2,3,4-tetrahydro-2-[[(1-methylethyl)amino]methyl]-7-nitro-6-quinolinemethanol) was submitted to the Mannich reaction, using formaldehyde, paraformaldehyde and acetaldehyde as reagents, and gave three unexpected products: two of them were cyclized on the alkylamine side chain and another etherified on the aminequinolinemethanol group. The three compounds were biologically evaluated using mice infected with Schistosoma mansoni and showed promising activities, but had higher toxicities. For studies on structure-activity relationships, results demonstrate that the side alkylamine group can be modified with preserved activity, but that this modification is associated with increased toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical / methods*
  • Male
  • Mice
  • Oxamniquine / analogs & derivatives*
  • Oxamniquine / chemical synthesis*
  • Oxamniquine / therapeutic use
  • Schistosomiasis mansoni / drug therapy
  • Schistosomicides / chemical synthesis*
  • Schistosomicides / therapeutic use
  • Structure-Activity Relationship

Substances

  • Schistosomicides
  • Oxamniquine