The physiological action of some furan compounds

Kirkpatrick, W. H.

doi:10.31274/rtd-180813-14499

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“…The affinities of all five compounds for both 5-HT 2 receptor subtypes were determined by radioligand displacement assays ([ 3 H]ketanserin for 5-HT 2A and [ 3 H]mesulergine for 5-HT 2C ), and the functional activities were assessed by a standard fluorescence assay, as Ca 2+ mobilization. The hydrochlorides of 2-(dibenzo[ b , d ]furan-2-yl)ethanamine ( 1 ) and 2-(dibenzo[ b , d ]furan-4-yl)ethanamine ( 3 ) had been synthesized by another route in the mid-1900s and only said to be “toxic”. , The results are shown in Table .…”

Section: Resultsmentioning

confidence: 99%

“…The hydrochlorides of 2-(dibenzo[b,d]furan-2-yl)ethanamine (1) and 2-(dibenzo-[b,d]furan-4-yl)ethanamine (3) had been synthesized by another route in the mid-1900s and only said to be "toxic". 12,13 The results are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…2-(Dibenzo[b,d]furan-2-yl)ethanamine Hydrochloride (1-HCl). 12,13 Yield: 72%; colorless solid; mp 225− 227 °C. 13 H]-ketanserin (47.3 Ci/mL, 1 mCi/mL, PerkinElmer NET791250UC) and HeLa-5-HT 2C cell membranes (cell line was generated in-house) (receptor expression = 150 fmol/mg protein, protein concentration = 2041 μg/mL) against [ 3 H]mesulergine (84.7 Ci/mL, 1 mCi/mL, PerkinElmer NET1148250UC).…”

Section: Methodsmentioning

confidence: 99%

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Dibenzofuranylethylamines as 5-HT_2A/2C Receptor Agonists

et al. 2020

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The human 5-HT 2 receptor subtypes have high sequence identity in their orthosteric ligand-binding domain, and many agonists are poorly selective between the 5-HT 2A and 5-HT 2C subtypes. Nevertheless, their activation is associated with different pharmacological outcomes. We synthesized five phenethylamine analogs in which the benzene ring is replaced by a bulky dibenzo[b,d]furan moiety and found a couple with >70fold 5-HT 2C selectivity. Molecular docking studies of the most potent compound (5) at both receptor subtypes revealed the likely structural basis of its selectivity. Although in both cases, some crucial interactions are conserved, the change of the Ala222 5.46 residue in the 5-HT 2C receptor to the larger Ser242 5.46 in the 5-HT 2A subtype, which is the only structural difference between the orthosteric binding pockets of both receptors, weakens a π−π stacking interaction between the dibenzofuran moiety and the important Phe 6.52 residue and breaks a hydrogen bond between the dibenzofuran oxygen and Ser 5.43 , explaining the selectivity of compound 5 for the 5-HT 2C receptor. We believe that this effect of the residue at position 5.46 merits further exploration in the search for selective 5-HT 2C receptor agonists that are of considerable interest in the treatment of schizophrenia and substance abuse.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%