Novel 2,3,4,5-tetrahydro-1H-3-benzazepines with high affinity and selectivity for the dopamine D3 receptor

N E Austin; K Y Avenell; I Boyfield; C L Branch; M S Hadley; P Jeffrey; C N Johnson; G J Macdonald; D J Nash; G J Riley; A B Smith; G Stemp; K M Thewlis; A K Vong; M Wood

doi:10.1016/s0960-894x(00)00505-9

Novel 2,3,4,5-tetrahydro-1H-3-benzazepines with high affinity and selectivity for the dopamine D3 receptor

Bioorg Med Chem Lett. 2000 Nov 20;10(22):2553-5. doi: 10.1016/s0960-894x(00)00505-9.

Authors

N E Austin¹, K Y Avenell, I Boyfield, C L Branch, M S Hadley, P Jeffrey, C N Johnson, G J Macdonald, D J Nash, G J Riley, A B Smith, G Stemp, K M Thewlis, A K Vong, M Wood

Affiliation

¹ SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.

PMID: 11086728
DOI: 10.1016/s0960-894x(00)00505-9

Abstract

Starting from the dopamine D3 receptor antagonist SB-277011 1, a series of 2,3,4,5-tetrahydro-1H-3-benzazepines has been identified with high affinity for the dopamine D3 receptor and selectivity over the D2 receptor. The 3-acetamido-2-fluorocinnamide derivative 20 gave high D3 receptor affinity (pKi 8.4) with 130-fold selectivity over the 2, receptor.

MeSH terms

Animals
Nitriles / chemistry
Nitriles / pharmacology*
Quinolines / chemistry
Quinolines / pharmacology*
Rats
Receptors, Dopamine D2 / drug effects*
Receptors, Dopamine D3
Tetrahydroisoquinolines*

Substances

Drd3 protein, rat
Nitriles
Quinolines
Receptors, Dopamine D2
Receptors, Dopamine D3
SB 277011
Tetrahydroisoquinolines