2-(1-Naphthyloxy)ethylamines with enhanced affinity for human 5-HT1D beta (h5-HT1B) serotonin receptors.
Article Details
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Ismaiel AM, Dukat M, Law H, Kamboj R, Fan E, Lee DK, Mazzocco L, Buekschkens D, Teitler M, Pierson ME, Glennon RA
2-(1-Naphthyloxy)ethylamines with enhanced affinity for human 5-HT1D beta (h5-HT1B) serotonin receptors.
J Med Chem. 1997 Dec 19;40(26):4415-9.
- PubMed ID
- 9435911 [ View in PubMed]
- Abstract
Although the beta-adrenergic antagonist propranolol (1) binds at rodent 5-HT1B serotonin receptors, it displays low affinity (Ki > 10,000 nM) for its species homologue 5-HT1D beta (i.e., h5-HT1B) receptors. The structure of propranolol was systematically modified in an attempt to enhance its affinity for the latter population of receptors. Removal of the alkyl hydroxyl group, shortening of the O-alkyl chain from three to two methylene groups, and variation of the terminal amine substituent resulted in compounds, such as N-monomethyl-2-(1-naphthyloxy)-ethylamine (11; Ki = 26 nM), that display significantly higher h5-HT1B affinity than propranolol. Compound 11 was shown to bind equally well at human 5-HT1D alpha (h5-HT1D) receptors (Ki = 34 nM) and was further demonstrated to possess h5-HT1B agonist character in an adenylate cyclase assay. It would appear that such (aryloxy)alkylamines may represent a novel class of 5-HT1D receptor agonists.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Pindolol 5-hydroxytryptamine receptor 1B Ki (nM) >10000 N/A N/A Details Pindolol 5-hydroxytryptamine receptor 1B Ki (nM) 2600 N/A N/A Details Propranolol 5-hydroxytryptamine receptor 1B Ki (nM) >10000 N/A N/A Details Propranolol 5-hydroxytryptamine receptor 1B Ki (nM) 4100 N/A N/A Details