Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists.

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Urbanek RA, Xiong H, Wu Y, Blackwell W, Steelman G, Rosamond J, Wesolowski SS, Campbell JB, Zhang M, Brockel B, Widzowski DV

Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists.

Bioorg Med Chem Lett. 2013 Jan 15;23(2):543-7. doi: 10.1016/j.bmcl.2012.11.023. Epub 2012 Nov 28.

PubMed ID
23237836 [ View in PubMed
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Abstract

Dopamine (D(2)) partial agonists (D2PAs) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics. Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D(2) partial agonists. These compounds have good selectivity, CNS drug-like properties and tunable D(2) partial agonism. One of the key compounds, 8h, has good in vitro/in vivo ADME characteristics, and is active in a rat amphetamine-induced locomotor activity model.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AripiprazoleDopamine D2 receptorIC 50 (nM)7.6N/AN/ADetails
AripiprazoleDopamine D2 receptorKi (nM)0.2N/AN/ADetails
BifeprunoxDopamine D2 receptorIC 50 (nM)2.9N/AN/ADetails
BifeprunoxDopamine D2 receptorKi (nM)0.6N/AN/ADetails
PramipexoleDopamine D2 receptorIC 50 (nM)>10000N/AN/ADetails