Synthesis and SAR of highly potent and selective dopamine D(3)-receptor antagonists: Quinolin(di)one and benzazepin(di)one derivatives. herve.geneste@abbott.com.

The synthesis and SAR of novel and selective dopamine D(3)-receptor antagonists based on a 3,4-dihydro-1H-quinolin-2-one, a 1,3,4,5-tetrahydro-benzo[b]azepin-2-one, 1H-quinoline-2,4-dione or a 3,4-dihydro-1H-benzo[b]azepine-2,5-dione scaffold are discussed. A706149 (2.15mg/kg, po) antagonizes PD 128907-induced huddling deficits in rat, a social interaction paradigm.

Synthesis and SAR of highly potent dual 5-HT1A and 5-HT1B antagonists as potential antidepressant drugs.

Novel 5-HT(1) autoreceptor ligands based on the N-4-aryl-piperazinyl-N'-ethyl-5,6,7,8-tetrahydropyrido[4', 3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one core are described. Aiming at antidepressants with a novel mode of action our objective was to identify potent antagonists showing balanced affinities and high selectivity for the 5-HT(1A) and 5-HT(1B) receptors. Strategies for the development of dual 5-HT(1A) and 5-HT(1B) antagonists based on 1 and 2 as leads and the corresponding results are discussed.