Title of article :
Novel 1,2,3,4-tetrahydroisoquinolines with high affinity and selectivity for the dopamine D3 receptor
Author/Authors :
Nigel E. Austin، نويسنده , , Kim Y. Avenell، نويسنده , , Izzy Boyfield، نويسنده , , Clive L. Branch، نويسنده , , Martyn C. Coldwell، نويسنده , , Michael S. Hadley، نويسنده , , Phillip Jeffrey، نويسنده , , Amana Johns، نويسنده , , Christopher N. Johnson، نويسنده , , David J. Nash، نويسنده , , Graham J. Riley، نويسنده , , Stephen A. Smith، نويسنده , , Rachel C. Stacey، نويسنده , , Geoffrey Stemp، نويسنده , , Kevin M. Thewlis، نويسنده , , Antonio K. K. Vong، نويسنده ,
Abstract :
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.
