Design and synthesis of D₁ agonist/D₂ antagonist for treatment of schizophrenia

Autor:	Andrew, Giovanni, Joachim, Roehr, Shannon, Dwyer, Kent, Neuenschwander, Anthony, Scotese, Neil D, Moorcroft, Larry, Davis, Zhongli, Gao
Rok vydání:	2012
Předmět:	Male Dopamine D2 Receptor Antagonists Mice Structure-Activity Relationship Receptors Dopamine D2 Drug Design Receptors Dopamine D1 Tetrahydroisoquinolines Schizophrenia Animals
Zdroj:	Bioorganicmedicinal chemistry letters. 23(5)
ISSN:	1464-3405
Popis:	A series of tetrahydroisoquinolines were designed, synthesized and evaluated as the first non-natural product type of compounds with dual D(1) receptor (D(1)R) agonism and D(2) receptor (D(2)R) antagonism properties for treatment of schizophrenia. The initial SAR of the series was explored. The lead in the series, 3g, exhibited high affinity and good potency. Compound 3g displayed 95% of D(1)R occupancy (10 mg/kg, sc) and 75% of D(2)R occupancy (10 mg/kg, sc) in the striatum of male CD-1 mice. The series exhibited unique pharmacology and merit as tool compounds for target validation and future optimizations.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::ec02b08879718f99ce9fd8e1b28318dd https://pubmed.ncbi.nlm.nih.gov/23333208 Zobrazit plný text záznamu Full Text from ScienceDirect