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

• Published in: Bioorganic & medicinal chemistry letters Vol. 15; no. 12; pp. 2990 - 2993
• Main Authors: Kamei, Katsuhide, Maeda, Noriko, Katsuragi-Ogino, Ryoko, Koyama, Makoto, Nakajima, Mika, Tatsuoka, Toshio, Ohno, Tomochika, Inoue, Teruyoshi
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2005
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.04.059

4-Methyl-2-(1,2,3,6-tetrahydropyridin-4-yl)pyrimidine derivative 23 ( SUN N5147) exhibited sub-nanomolar affinity for 5-HT 1A receptor with 1000-fold selectivity over both dopamine D 2 and α 1-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion model. 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-HT 1A receptor with 1000-fold selectivity over both dopamine D 2 and α 1-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.