New piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives as selective 5-HT1A receptor agonists with highly potent anti-ischemic effects

Bioorg Med Chem Lett. 2005 Jun 15;15(12):2990-3. doi: 10.1016/j.bmcl.2005.04.059.

Abstract

A series of new piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives were synthesized. Among these compounds, 4-methyl-2-(1,2,3,6-tetrahydropyridin-4-yl)pyrimidine derivative 23 (SUN N5147) exhibited sub-nanomolar affinity for 5-HT1A receptor with 1000-fold selectivity over both dopamine D2 and alpha1-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists
  • Animals
  • Arterial Occlusive Diseases / drug therapy
  • Arterial Occlusive Diseases / metabolism
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism
  • Cerebrovascular Circulation / drug effects*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / pharmacology*
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Rats
  • Receptors, Dopamine D2 / agonists
  • Serotonin 5-HT1 Receptor Agonists*
  • Serotonin Receptor Agonists / chemical synthesis
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Neuroprotective Agents
  • Piperazines
  • Pyrimidines
  • Receptors, Dopamine D2
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin Receptor Agonists
  • pyrimidine