Abstract
Investigation of conformationally restricted benzamide bioisosteres led to the chiral phenyltetrahydropyrimidine derivative ent2a (FAUC 312) displaying strong and highly selective dopamine D4 receptor binding (K(i(high))=1.5 nM). Mitogenesis experiments indicated 83% ligand efficacy when compared to the unselective agonist quinpirole. The target compounds of type 2 and 3 were synthesized in enantiopure form starting from asparagine.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amidines / chemistry*
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Animals
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Benzamides / chemistry*
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CHO Cells
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Cattle
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Clozapine / pharmacology
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Cricetinae
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Cyclization
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Humans
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Kinetics
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Ligands
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Mitogens / pharmacology
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Mitosis / drug effects
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Piperazines / chemical synthesis*
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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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Quinpirole / pharmacology
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Receptors, Dopamine D2 / agonists*
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Receptors, Dopamine D2 / metabolism
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Receptors, Dopamine D4
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Amidines
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Benzamides
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DRD4 protein, human
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FAUC 312
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Ligands
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Mitogens
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Piperazines
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Pyrimidines
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Receptors, Dopamine D2
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Receptors, Dopamine D4
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Quinpirole
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benzamide
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Clozapine