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

Authors
Austin, NE Avenell, KY Boyfield, I Branch, CL Hadley, MS Jeffrey, P Johnson, CN Macdonald, GJ Nash, DJ Riley, GJ Smith, AB Stemp, G Thewlis, KM Vong, AKK Wood, MD
Citation
Ne. Austin et al., Design and synthesis of novel 2,3-dihydro-1H-isoindoles with high affinityand selectivity for the dopamine D-3 receptor, BIOORG MED, 11(5), 2001, pp. 685-688
Citations number
10
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
5
Year of publication
2001
Pages
685 - 688
Database
ISI
SICI code
0960-894X(20010312)11:5<685:DASON2>2.0.ZU;2-D
Abstract
Starting from the tetrahydroisoquinoline SB-277011 1, a novel series of 5-s ubstituted-2,3-dihydro-1H-isoindoles has been designed. Subsequent optimisa tion resulted in identification of 19, which has high affinity for the dopa mine D-3 receptor (pK(i) 8.3) and greater than or equal to 100-fold selecti vity over other aminergic receptors. In rat studies 19 was brain penetrant with an excellent pharmacokinetic profile (oral bioavailability 77%, t(1/2) 5.2 h). (C) 2001 Elsevier Science Ltd. All rights reserved.