Novel 1,2,3,4-tetrahydroisoquinolines with high affinity and selectivity for the dopamine D-3 receptor

Authors
Austin, NE Avenell, KY Boyfield, I Branch, CL Coldwell, MC Hadley, MS Jeffrey, P Johns, A Johnson, CN Nash, DJ Riley, GJ Smith, SA Stacey, RC Stemp, G Thewlis, KM Vong, AKK
Citation
Ne. Austin et al., Novel 1,2,3,4-tetrahydroisoquinolines with high affinity and selectivity for the dopamine D-3 receptor, BIOORG MED, 9(2), 1999, pp. 179-184
Citations number
4
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
9
Issue
2
Year of publication
1999
Pages
179 - 184
Database
ISI
SICI code
0960-894X(19990118)9:2<179:N1WHAA>2.0.ZU;2-L
Abstract
Using clearance and brain penetration studies as a screen, tetrahydroisoqui noline 3 was identified as a lead having low clearance in rats (CLb 20 ml/m in/kg). Introduction of a 7-CF3SO2O- substituent into the tetrahydroisoquin oline, followed by replacement of the biphenylamido group of 3 by a 3-indol ylpropenamido group gave 31, having high D-3 receptor affinity (pKi 8.4) an d 150 fold selectivity over the D-2 receptor. (C) 1999 Elsevier Science Ltd . All rights reserved.