Synthesis and Structure−Affinity Relationships of 1-[ω-(4-Aryl-1-piperazinyl)alkyl]-1-aryl Ketones as 5-HT7Receptor Ligands
- 18 January 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 46 (4) , 646-649
- https://doi.org/10.1021/jm020994z
Abstract
Structural requirements for 5-HT7 receptor affinity and selectivity over that for the 5-HT1A receptor were studied on a series of 1-[ω-(4-aryl-1-piperazinyl)alkyl]-1-aryl ketones. The presence of a hydroxy or methoxy substituent on aryl ketone moiety, alkyl chain length, and the nature of N-1-piperazine substituent were explored. 6-[4-(3-Benzisoxazolyl)-1-piperazinyl]-1-(2-hydroxyphenyl)-1-hexanone (40) and its methoxy analogue 43 exhibited high 5-HT7 receptor affinities (Ki = 2.93 nM and 0.90 nM, respectively) and agonist properties when tested for 5-HT7 receptor-mediated relaxation of substance P-induced guinea-pig ileum contraction.Keywords
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