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

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.

• Authors: Katsuhide Kamei, Noriko Maeda, Ryoko Katsuragi-Ogino, Makoto Koyama, Mika Nakajima, Toshio Tatsuoka, Tomochika Ohno, Teruyoshi Inoue
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 15 Issue 12 Pg. 2990-3 (Jun 15 2005) ISSN: 0960-894X [Print] England
• PMID: 15914001 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

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