Butyrophenone analogues in the carbazole series as potential atypical antipsychotics:: synthesis and determination of affinities at D2, 5-HT2A, 5-HT2B and 5-HT2C receptors

We describe practical and efficient routes for synthesis of 2-aminomethyl-1,2,3,9-tetrahydro-4H-carbazol-4-ones using the Fischer indole synthesis or palladium-catalysed cyclization methodologies, as well as their affinities for D-2, 5-HT2A and 5-HT2C receptors, and their activity at the 5-HT2B receptor. The most active compounds, 4b (QF 2003B) and 4c (QF 2004B), with a pK(i) (5-HT2A/D-2) ratio of 1.28 show a potential antipsychotic profile according to Meltzer's classification. (C) 2000 Editions scientifiques et medicales Elsevier SAS.