Syntheses and properties of the major hydroxy metabolites in humans of blonanserin AD-5423, a novel antipsychotic agent

Bioorg Med Chem Lett. 2005 Feb 15;15(4):1055-9. doi: 10.1016/j.bmcl.2004.12.028.

Abstract

Two major metabolites in humans of blonanserin, 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta-[b]pyridine (code name AD-5423), were synthesized. The first, 7-hydroxylated AD-5423, was synthesized through a four-step process starting from 4-fluorobenzoylacetonitrile (1), and the second, 8-hydroxylated AD-5423, a nine-step process also from 1. The optical resolution, structures, and receptor binding properties of the metabolites were documented.

MeSH terms

  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / metabolism
  • Antipsychotic Agents / pharmacology
  • Humans
  • Microsomes, Liver / metabolism
  • Piperazines / chemical synthesis*
  • Piperazines / metabolism
  • Piperazines / pharmacology
  • Piperidines / chemical synthesis*
  • Piperidines / metabolism
  • Piperidines / pharmacology
  • Receptor, Serotonin, 5-HT2A / chemistry
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Receptors, Dopamine D2 / chemistry
  • Receptors, Dopamine D2 / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Piperazines
  • Piperidines
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2
  • dopamine D2L receptor
  • blonanserin