Abstract
Structural requirements for 5-HT(7) receptor affinity and selectivity over that for the 5-HT(1A) receptor were studied on a series of 1-[omega-(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-HT(7) receptor affinities (Ki = 2.93 nM and 0.90 nM, respectively) and agonist properties when tested for 5-HT(7) receptor-mediated relaxation of substance P-induced guinea-pig ileum contraction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / metabolism
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Cell Line
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Cricetinae
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Guinea Pigs
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Humans
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Ileum / drug effects
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Ileum / physiology
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In Vitro Techniques
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Isoxazoles / chemical synthesis*
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Isoxazoles / chemistry
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Isoxazoles / pharmacology
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Ketones / chemical synthesis*
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Ketones / chemistry
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Ketones / pharmacology
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Ligands
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Liver / metabolism
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Radioligand Assay
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Rats
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Receptors, Serotonin / metabolism*
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Structure-Activity Relationship
Substances
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6-(4-(3-benzisoxazolyl)-1-piperazinyl)-1-(2-hydroxyphenyl)-1-hexanone
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6-(4-(3-benzisoxazolyl)-1-piperazinyl)-1-(2-methoxyphenyl)-1-hexanone
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Isoxazoles
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Ketones
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Ligands
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Piperazines
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Receptors, Serotonin
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serotonin 7 receptor