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ID: ALA1132014

Journal: Bioorg Med Chem Lett

Title: Novel 1,2,3,4-tetrahydroisoquinolines with high affinity and selectivity for the dopamine D3 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 AK.

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.

CiteXplore: 10021923

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