Design and synthesis of novel 2,3-dihydro-1H-isoindoles with high affinity and selectivity for the dopamine D3 receptor

Autor:	Gregor James Macdonald, Phillip Jeffrey, Nigel E. Austin, Vong Antonio Kuok Keong, Graham J. Riley, Izzy Boyfield, Christopher N. Johnson, Alexander Baxter Smith, Clive Leslie Branch, Geoffrey Stemp, Kim Y. Avenell, Michael S. Hadley, Kevin M. Thewlis, Martyn D. Wood, David John Nash
Rok vydání:	2001
Předmět:	Models Molecular Indoles Isoindoles Stereochemistry medicine.drug_class Clinical Biochemistry Pharmaceutical Science Carboxamide CHO Cells Biochemistry Chemical synthesis Radioligand Assay chemistry.chemical_compound Dopamine receptor D3 Cricetinae Drug Discovery medicine Animals Humans Receptor Molecular Biology Molecular Structure Receptors Dopamine D2 Chemistry Tetrahydroisoquinoline Organic Chemistry Receptors Dopamine D3 Brain Rats Bioavailability Drug Design Dopamine Antagonists Molecular Medicine Selectivity
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 11:685-688
ISSN:	0960-894X
DOI:	10.1016/s0960-894x(01)00037-3
Popis:	Starting from the tetrahydroisoquinoline SB-277011 1, a novel series of 5-substituted-2,3-dihydro-1H-isoindoles has been designed. Subsequent optimisation resulted in identification of 19, which has high affinity for the dopamine D3 receptor (pKi 8.3) and > or = 100-fold selectivity over other aminergic receptors. In rat studies 19 was brain penetrant with an excellent pharmacokinetic profile (oral bioavailability 77%, t1/2 5.2h).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48ececfdc04651e6149733a9695bddb3 https://doi.org/10.1016/s0960-894x(01)00037-3 Zobrazit plný text záznamu Full Text from ScienceDirect