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Synthesis and SAR of highly potent dual 5-HT1A and 5-HT 1B antagonists as potential antidepressant drugs
Novel 5-HT1 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-HT1B receptors. Strategies for the development of dual 5-HT1A and 5-HT1B antagonists based on 1 and 2 as leads and the corresponding results are discussed. Isoquinoline analogue 33 displayed high affinity and an antagonistic mode of action for the 5-HT 1A and the 5-HT1B receptors and was characterized further with respect to selectivity, electrically stimulated [3H]5-HT release and in vivo efficacy.
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Reference£º
Benzofuran – Wikipedia,
Benzofuran | C8H2204O – PubChem