title: Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists.
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.
authors.affiliation: CNS Discovery, AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Urbanek
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: William
authors.initials: W
authors.lastname: Blackwell
authors.forename: Gary
authors.initials: G
authors.lastname: Steelman
authors.forename: Jim
authors.initials: J
authors.lastname: Rosamond
authors.forename: Steven S
authors.initials: SS
authors.lastname: Wesolowski
authors.forename: James B
authors.initials: JB
authors.lastname: Campbell
authors.forename: Minli
authors.initials: M
authors.lastname: Zhang
authors.forename: Becky
authors.initials: B
authors.lastname: Brockel
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Widzowski
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001681:Biological Assay; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054333:Drug Partial Agonism; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2