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.
Rebecca A Urbanek  1 ,  Hui Xiong ,  Ye Wu ,  William Blackwell ,  Gary Steelman ,  Jim Rosamond ,  Steven S Wesolowski ,  James B Campbell ,  Minli Zhang ,  Becky Brockel ,  Daniel V Widzowski
Affiliations
  • 1. CNS Discovery, AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE, USA.
PMID: 23237836 DOI: 10.1016/j.bmcl.2012.11.023
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.