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Artigo Revisado por pares
BIBTEX RIS

Novel 1,2,3,4-tetrahydroisoquinolines with high affinity and selectivity for the dopamine D3 receptor

1999; Elsevier BV; Volume: 9; Issue: 2 Linguagem: Inglês

10.1016/s0960-894x(98)00699-4

ISSN

1464-3405

Autores

Nigel Austin, Kim Y. Avenell, Izzy Boyfield, Clive L. Branch, Martyn C. Coldwell, Michael S. Hadley, Philip D. Jeffrey, Amana Johns, Christopher N. Johnson, David J. Nash, Graham J. Riley, Stephen A. Smith, Rachel Stacey, Geoffrey Stemp, Kevin M. Thewlis, Antonio Vong,

Tópico(s)

Neuropeptides and Animal Physiology

Resumo

Using clearance and brain penetration studies as a screen, tetrahydroisoquinoline 3 was identified as a lead having low clearance in rats (CLb 20 ml/min/kg). Introduction of a 7-CF3SO2O- substituent into the tetrahydroisoquinoline, followed by replacement of the biphenylamido group of 3 by a 3-indolylpropenamido group gave 31, having high D3 receptor affinity (pKi 8.4) and 150 fold selectivity over the D2 receptor.

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