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