Synthesis and SAR of highly potent and selective dopamine D3-receptor antagonists: Variations on the 1H-pyrimidin-2-one theme
Graphical abstract
Synthesis and SAR of highly potent and selective D3 antagonists based on a 1H-pyridin-2-one or on a urea scaffold are described. Thus, 7b displays oral bioavailability as well as brain penetration in rat. These data significantly enhance our understanding of the D3 pharmacophore and are expected to lead to novel approaches for the treatment of schizophrenia.
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Acknowledgments
We thank Stefan Maurus, Karlpeter Orth, Katerina Sarris, and Sonja Triebel for supporting chemical synthesis, our analytical department, Manfred Nebel, Heidrun Gärtner, and Beate Rauprich for assay development and screening, Sylvia Hellwig for the permeability measurements (Caco-2).
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