Synthesis and biological evaluation of new quinazoline and cinnoline derivatives as potential atypical antipsychotics

Chem Biodivers. 2006 Jan;3(1):106-17. doi: 10.1002/cbdv.200690001.

Abstract

Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized (Schemes 2 and 3), and evaluated for their binding affinities (Table) towards the serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new compounds, the quinazoline derivative 15 (= 7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (= 7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5-one) displayed high selectivity in its binding profile towards the 5-HT2C compared to both the 5-HT2A and D2 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / chemical synthesis*
  • Antipsychotic Agents / isolation & purification
  • Antipsychotic Agents / metabolism
  • Heterocyclic Compounds, 2-Ring / chemical synthesis*
  • Heterocyclic Compounds, 2-Ring / isolation & purification
  • Heterocyclic Compounds, 2-Ring / metabolism
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Quinazolines / chemical synthesis*
  • Quinazolines / isolation & purification
  • Quinazolines / metabolism
  • Receptors, Dopamine / metabolism
  • Receptors, Serotonin / metabolism

Substances

  • Antipsychotic Agents
  • Heterocyclic Compounds, 2-Ring
  • Quinazolines
  • Receptors, Dopamine
  • Receptors, Serotonin
  • cinnoline