Benzofuran Bioisosteres of Hallucinogenic Tryptamines

Zbigniew Tomaszewski, Michael P. Johnson, Xuemei Huang, David E. Nichols

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The benzofuran analogues of the hallucinogens 5-methoxy-N,N-dimethyltryptamine and 5-methoxy-α-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-HT2 receptor. It is suggested that benzofurans may be useful in the design of serotonin receptor ligands.

Original languageEnglish (US)
Pages (from-to)2061-2064
Number of pages4
JournalJournal of Medicinal Chemistry
Volume35
Issue number11
DOIs
StatePublished - May 1 1992

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Benzofurans
Tryptamines
Receptor, Serotonin, 5-HT1A
Amines
Methoxydimethyltryptamines
Hallucinogens
Indoles
8-Hydroxy-2-(di-n-propylamino)tetralin
Serotonin Receptors
Serotonin
Ligands
Brain
benzofuran
indole

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Tomaszewski, Zbigniew ; Johnson, Michael P. ; Huang, Xuemei ; Nichols, David E. / Benzofuran Bioisosteres of Hallucinogenic Tryptamines. In: Journal of Medicinal Chemistry. 1992 ; Vol. 35, No. 11. pp. 2061-2064.
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abstract = "The benzofuran analogues of the hallucinogens 5-methoxy-N,N-dimethyltryptamine and 5-methoxy-α-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-HT2 receptor. It is suggested that benzofurans may be useful in the design of serotonin receptor ligands.",
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Tomaszewski, Z, Johnson, MP, Huang, X & Nichols, DE 1992, 'Benzofuran Bioisosteres of Hallucinogenic Tryptamines', Journal of Medicinal Chemistry, vol. 35, no. 11, pp. 2061-2064. https://doi.org/10.1021/jm00089a017

Benzofuran Bioisosteres of Hallucinogenic Tryptamines. / Tomaszewski, Zbigniew; Johnson, Michael P.; Huang, Xuemei; Nichols, David E.

In: Journal of Medicinal Chemistry, Vol. 35, No. 11, 01.05.1992, p. 2061-2064.

Research output: Contribution to journalArticle

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