Radiochemical synthesis and biodistribution of a novel maxi-K potassium channel opener

Nucl Med Biol. 2002 Jan;29(1):55-9. doi: 10.1016/s0969-8051(01)00281-5.

Abstract

The racemate 1, ((+/-)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)- 2H-indol-2-one), is a potent, specific and novel opener of cloned large-conductance, calcium-activated (maxi-K) potassium channels. One of its enantiomers, BMS-204352 (MaxiPost), is undergoing clinical evaluation for efficacy in patients with suspected acute stroke. In the current study, we have prepared [(18)F]-labeled 1 using a silver assisted nucleophilic substitution to examine its distribution and disposition in the rat, with particular emphasis on the brain. Biodistribution studies in rats confirm that brain uptake is rapid and occurs at high levels, and indicate that a major fraction of the compound in the brain does not accumulate by a specific, saturable mechanism.

MeSH terms

  • Animals
  • Brain / metabolism
  • Indoles / chemical synthesis*
  • Indoles / pharmacokinetics
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / pharmacokinetics
  • Potassium Channels / drug effects
  • Rats
  • Tissue Distribution

Substances

  • BMS204352
  • Indoles
  • Neuroprotective Agents
  • Potassium Channels