Short and efficient syntheses of analogues of WAY-100635: New and potent 5-HT1A receptor antagonists

Simple syntheses of four new and potent analogues of the 5-HT1A receptor li gand, WAY-100635 are described, namely the 6-(pyridinyl)-bromo-, the 6-(pyr idinyl)-fluoro-, the pyrimidine- and the 5-(pyridinyl)-bromo-analogues. The first three analogues were obtained by aromatic nucleophilic substitution of the 2,6-dihalogenopyridine (activated or not as an N-oxide) or of the 2- chloropyrimidine with the corresponding amine nucleophile as a key step. Th e fourth analogue, the 5-(pyridinyl)-bromo-analogue, was synthesized from t he 2-amino-5-bromopyridine via a progressive elongation of the skeleton. Th e four compounds described are all full antagonists and show good in vitro binding affinities (K-i). (C) 2001 Elsevier Science Ltd. All rights reserve d.