New 1,2,3,9-tetrahydro-4H-carbazol-4-one derivatives: analogues of HEAT as ligands for the alpha1-adrenergic receptor subtypes

Bioorganic & Medicinal Chemistry
Giuseppe RomeoKenneth P Minneman

Abstract

With the aim to develop new ligands able to discriminate among the three subtypes of alpha1-adrenergic receptors (alpha1A-AR, alpha1B-AR, and alpha1D-AR), a series of new 1,2,3,9-tetrahydro-4H-carbazol-4-ones bearing a 3-[[[2-(4-hydroxyphenyl)ethyl]amino]methyl] or a 3-[[4-(2-substitutedphenyl)piperazin-1-yl]methyl] side chain were synthesized. The general structure of the new compounds is reminiscent of HEAT and RN5, two potent alpha1-AR antagonists which show high affinities for all three alpha1-AR subtypes. Some derivatives in which one ring of the tetrahydrocarbazolone system was opened were also prepared. Compounds were tested in radioligand binding assays on human cloned alpha1A-AR, alpha1B-AR, and alpha1D-AR subtypes stably expressed in HEK293 cells. They showed moderate to good affinities, although their selectivity among the receptor subtypes hardly reached one order of magnitude.

References

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Jun 27, 2003·Journal of Medicinal Chemistry·Giuseppe RomeoKenneth P Minneman

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Citations

Aug 8, 2008·Chemical Communications : Chem Comm·Veejendra K Yadav, Naganaboina Vijaya Kumar
Dec 3, 2014·European Journal of Medicinal Chemistry·Gheorghe Roman
Feb 4, 2010·Chemical Communications : Chem Comm·Kaliyappan MuruganChinpiao Chen
Jan 24, 2014·Acta Crystallographica. Section E, Structure Reports Online·Mustafa GöçmentürkTuncer Hökelek

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