Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists.
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Hansen M, Phonekeo K, Paine JS, Leth-Petersen S, Begtrup M, Brauner-Osborne H, Kristensen JL
Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists.
ACS Chem Neurosci. 2014 Mar 19;5(3):243-9. doi: 10.1021/cn400216u. Epub 2014 Jan 15.
- PubMed ID
- 24397362 [ View in PubMed]
- Abstract
N-Benzyl substitution of 5-HT2A receptor agonists of the phenethylamine structural class of psychedelics (such as 4-bromo-2,5-dimethoxyphenethylamine, often referred to as 2C-B) confer a significant increase in binding affinity as well as functional activity of the receptor. We have prepared a series of 48 compounds with structural variations in both the phenethylamine and N-benzyl part of the molecule to determine the effects on receptor binding affinity and functional activity at 5-HT2A and 5-HT2C receptors. The compounds generally had high affinity for the 5-HT2A receptor with 8b having the highest affinity at 0.29 nM but with several other compounds also exhibiting subnanomolar binding affinities. The functional activity of the compounds was distributed over a wider range with 1b being the most potent at 0.074 nM. Most of the compounds exhibited low to moderate selectivity (1- to 40-fold) for the 5-HT2A receptor in the binding assays, although one compound 6b showed an impressive 100-fold selectivity for the 5-HT2A receptor. In the functional assay, selectivity was generally higher with 1b being more than 400-fold selective for the 5-HT2A receptor.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine 5-hydroxytryptamine receptor 2A Protein Humans UnknownAgonistDetails