Cannabimimetic Activity of Novel Enantiomeric, Benzofuran Cannabinoids

Raphael Mechoulam; Aviva Breuer; Tobjorn U.C. Järbe; Arto J. Hiltunen; Robert Glaser

doi:10.1021/jm00165a024

Cannabimimetic Activity of Novel Enantiomeric, Benzofuran Cannabinoids

Raphael Mechoulam, Aviva Breuer, Tobjorn U.C. Järbe, Arto J. Hiltunen, Robert Glaser

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

The synthesis of the (2R,3R,4S,6R)-7/(2S,3S,4R,6S)-8 enantiomeric pair of benzofuran cannabinoids is reported together with the ¹H and ¹³C NMR spectral parameters. In benzofuran 8 the configurational arrangement of ligated groups at the stereogenic C(3) atom (through which the terpene moiety is connected to the aromatic ring) is very similar to that of the corresponding atom in natural (3R,4R)-Δ¹tetrahydrocannabinol (Δ¹THC), although their respective Cahn-Ingold-Prelog descriptors are different. In drug-discrimination tests in pigeons and rats, benzofuran 8 is as active as Δ¹-THC; in the mouse ring test compound 8 is more active than Δ⁶-THC. Enantiomer 7 is considerably less active than enantiomer 8 in both tests. These results can be explained by the fact that both 7 and 8 have a dimethylheptyl side chain (which is known to enhance cannabimimetic activity) and that Δ¹-THC and benzofuran 8 have closely related conformations, as determined by molecular mechanics.

Original language	English
Pages (from-to)	1037-1043
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	33
Issue number	3
DOIs	https://doi.org/10.1021/jm00165a024
State	Published - 1 Jan 1990

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Cannabimimetic Activity of Novel Enantiomeric, Benzofuran Cannabinoids",

abstract = "The synthesis of the (2R,3R,4S,6R)-7/(2S,3S,4R,6S)-8 enantiomeric pair of benzofuran cannabinoids is reported together with the 1H and 13C NMR spectral parameters. In benzofuran 8 the configurational arrangement of ligated groups at the stereogenic C(3) atom (through which the terpene moiety is connected to the aromatic ring) is very similar to that of the corresponding atom in natural (3R,4R)-Δ1tetrahydrocannabinol (Δ1THC), although their respective Cahn-Ingold-Prelog descriptors are different. In drug-discrimination tests in pigeons and rats, benzofuran 8 is as active as Δ1-THC; in the mouse ring test compound 8 is more active than Δ6-THC. Enantiomer 7 is considerably less active than enantiomer 8 in both tests. These results can be explained by the fact that both 7 and 8 have a dimethylheptyl side chain (which is known to enhance cannabimimetic activity) and that Δ1-THC and benzofuran 8 have closely related conformations, as determined by molecular mechanics.",

author = "Raphael Mechoulam and Aviva Breuer and J{\"a}rbe, {Tobjorn U.C.} and Hiltunen, {Arto J.} and Robert Glaser",

year = "1990",

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doi = "10.1021/jm00165a024",

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AU - Mechoulam, Raphael

AU - Breuer, Aviva

AU - Järbe, Tobjorn U.C.

AU - Hiltunen, Arto J.

AU - Glaser, Robert

PY - 1990/1/1

Y1 - 1990/1/1

N2 - The synthesis of the (2R,3R,4S,6R)-7/(2S,3S,4R,6S)-8 enantiomeric pair of benzofuran cannabinoids is reported together with the 1H and 13C NMR spectral parameters. In benzofuran 8 the configurational arrangement of ligated groups at the stereogenic C(3) atom (through which the terpene moiety is connected to the aromatic ring) is very similar to that of the corresponding atom in natural (3R,4R)-Δ1tetrahydrocannabinol (Δ1THC), although their respective Cahn-Ingold-Prelog descriptors are different. In drug-discrimination tests in pigeons and rats, benzofuran 8 is as active as Δ1-THC; in the mouse ring test compound 8 is more active than Δ6-THC. Enantiomer 7 is considerably less active than enantiomer 8 in both tests. These results can be explained by the fact that both 7 and 8 have a dimethylheptyl side chain (which is known to enhance cannabimimetic activity) and that Δ1-THC and benzofuran 8 have closely related conformations, as determined by molecular mechanics.

AB - The synthesis of the (2R,3R,4S,6R)-7/(2S,3S,4R,6S)-8 enantiomeric pair of benzofuran cannabinoids is reported together with the 1H and 13C NMR spectral parameters. In benzofuran 8 the configurational arrangement of ligated groups at the stereogenic C(3) atom (through which the terpene moiety is connected to the aromatic ring) is very similar to that of the corresponding atom in natural (3R,4R)-Δ1tetrahydrocannabinol (Δ1THC), although their respective Cahn-Ingold-Prelog descriptors are different. In drug-discrimination tests in pigeons and rats, benzofuran 8 is as active as Δ1-THC; in the mouse ring test compound 8 is more active than Δ6-THC. Enantiomer 7 is considerably less active than enantiomer 8 in both tests. These results can be explained by the fact that both 7 and 8 have a dimethylheptyl side chain (which is known to enhance cannabimimetic activity) and that Δ1-THC and benzofuran 8 have closely related conformations, as determined by molecular mechanics.

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DO - 10.1021/jm00165a024

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Cannabimimetic Activity of Novel Enantiomeric, Benzofuran Cannabinoids

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