Benzofuran bioisosteres of hallucinogenic tryptamines.
Z Tomaszewski, M P Johnson, X Huang, D E Nichols
Journal of Medicinal Chemistry May 1, 1992 DOI: 10.1021/jm00089a017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro receptor binding study Peer reviewed |
|---|---|
| Population | Rat brain homogenate |
| Measures | [125I]DOI, [3H]-8-OH-DPAT |
| Keywords | Hippocampus Frontal lobe Animals Rats, inbred strains Tryptamines Ethylamines Amphetamines Benzofurans Tetrahydronaphthalenes 8-hydroxy-2-di-n-propylaminotetralin Receptors, serotonin Serotonin antagonists Hallucinogens Molecular structure Structure-activity relationship Male |
| Key points | Replacing the indole of two methoxy-substituted hallucinogen analogues with a benzofuran reduced 5-HT2 receptor affinity to roughly one-third (primary amines) or one-sixth (tertiary amines) of the indole values, while 5-HT1A affinity dropped only about 20-30%. The authors suggest benzofurans may be useful in designing serotonin receptor ligands. |
Abstract
The benzofuran analogues of the hallucinogens 5-methoxy-N,N-dimethyltryptamine and 5-methoxy-alpha-methyltryptamine were synthesized and evaluated for affinity at the serotonin 5-HT2 and 5-HT1A receptors in rat brain homogenate, labeled with [125I]-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ([125I]DOI) and [3H]-8-hydroxy-2-(N,N-di-n-propylamino)tetralin ([3H]-8-OH-DPAT), respectively. At the 5-HT2 receptor, the benzofurans had slightly decreased affinities, approximately one-third and one-sixth those of the indoles, for the primary amines and the tertiary amines, respectively. The benzofurans also had lower affinity at the 5-HT1A receptor, but decreased only about 20-30% from that of the indole isosteres. Thus, the 5-HT1A receptor is less discriminating with respect to preference for an indole versus a benzofuran, although all of the compounds did have higher affinities for the 5-HT2 receptor than for the 5-HT1A receptor. It is suggested that benzofurans may be useful in the design of serotonin receptor ligands.
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- Recreational Use, Analysis and Toxicity of Tryptamines Current Neuropharmacology December 10, 2014
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- Delirium Due to Intoxication from the Novel Synthetic Tryptamine 5‐MeO‐DALT Journal of Forensic Sciences December 13, 2013
- Thieno[3,2-b]- and Thieno[2,3-b]pyrrole Bioisosteric Analogues of the Hallucinogen and Serotonin Agonist N,N-Dimethyltryptamine Journal of Medicinal Chemistry March 1, 1999
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