Marchais S, Nowicki B, Wikström H, Brennum L T, Halldin C, Pike V W
Department of Medicinal Chemistry, University Center for Pharmacy, University of Groningen, The Netherlands.
Bioorg Med Chem. 2001 Mar;9(3):695-702. doi: 10.1016/s0968-0896(00)00287-x.
Simple syntheses of four new and potent analogues of the 5-HT1A receptor ligand, WAY-100635 are described, namely the 6-(pyridinyl)-bromo-, the 6-(pyridinyl)-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. The fourth analogue, the 5-(pyridinyl)-bromo-analogue, was synthesized from the 2-amino-5-bromopyridine via a progressive elongation of the skeleton. The four compounds described are all full antagonists and show good in vitro binding affinities (Ki).
