A series of tryptamine analogues bearing a cyclopropylamine unit was prepared, starting from 3-indolyl acetonitriles, through a MeTi(Oi-Pr) 3 -mediated cyclopropanation.

Conformational restrictions: Based on the pharmacophore model for 5-HT(6) receptor ligands (shown), tryptamine analogues bearing a cyclopropyl ring on the α-position of the tryptamine side chain were synthesized and evaluated against 5-HT receptors. N,N-Dimethyl-1-arylsulfonyltryptamine derivatives exhibited promising selectivity for 5-HT(6) over 5-HT(1a) and 5-HT(4) receptors and interesting activity against 5-HT(6) (K(i) =∼0.15 μM; IC(50) =∼0.20 μM).

Several synthetic strategies were developed for the preparation of highly substituted pyrido[2,3-d]pyridazines. We particularly focused on the impact of the pyridine nitrogen atom on pyridazine ring reactivity toward aromatic substitutions, alkylations, or pallado-catalyzed cross-coupling reactions.

Synthesis of New Cyclopropanated Tryptamine Analogues. -A new series of N,N-dimethyltryptamine analogues (III) is prepared by a MeTi(OiPr) 3 -promoted cyclopropanation starting from 3-indolyl acetonitriles (I). Investigations concerning the 5-HT6 binding affinity of (III) are in progress. -(SZALATA, C.; SAPI, J.; SZYMONIAK, J.; BERTUS, P.; GERARD*, S.; Synlett 2008, 10, 1479-1482; Fac. Pharm., Inst. Chim. Mol., CNRS, Univ. Reims-Champagne-Ardenne, F-51096 Reims, Fr.; Eng.) -M. Paetzel 43-124