ω-(Imidazol-4-yl)alkane-1-sulfonamides: a new series of potent histamine H3 receptor antagonists

Tozer, Matthew J.; Buck, Ildiko M.; Cooke, Tracey; Kalindjian, S. Barret; Pether, Michael J.; Steel, Katherine I. M.

doi:10.1016/s0968-0896(01)00295-4

Cited by 11 publications

(2 citation statements)

References 24 publications

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“…For the longer-chain alkyne homologue of (un)protected 23 , we sought to apply a similar sequence as for 23 . The required aldehyde 26 was prepared through modification of a reported procedure . It involves a Wittig reaction to give 25 followed by hydrogenation and aldehyde deprotection.…”

Section: Resultsmentioning

confidence: 99%

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Triazole Ligands Reveal Distinct Molecular Features That Induce Histamine H₄ Receptor Affinity and Subtly Govern H₄/H₃ Subtype Selectivity

et al. 2011

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The histamine H(3) (H(3)R) and H(4) (H(4)R) receptors attract considerable interest from the medicinal chemistry community. Given their relatively high homology yet widely differing therapeutic promises, ligand selectivity for the two receptors is crucial. We interrogated H(4)R/H(3)R selectivities using ligands with a [1,2,3]triazole core. Cu(I)-assisted "click chemistry" was used to assemble diverse [1,2,3]triazole compounds (6a-w and 7a-f), many containing a peripheral imidazole group. The imidazole ring posed some problems in the click chemistry putatively due to Cu(II) coordination, but Boc protection of the imidazole and removal of oxygen from the reaction mixture provided effective strategies. Pharmacological studies revealed two monosubstituted imidazoles (6h,p) with <10 nM H(4)R affinities and >10-fold H(4)R/H(3)R selectivity. Both compounds possess a cycloalkylmethyl group and appear to target a lipophilic pocket in H(4)R with high steric precision. The use of the [1,2,3]triazole scaffold is further demonstrated by the notion that simple changes in spacer length or peripheral groups can reverse the selectivity toward H(3)R. Computational evidence is provided to account for two key selectivity switches and to pinpoint a lipophilic pocket as an important handle for H(4)R over H(3)R selectivity.

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Section: Resultsmentioning

confidence: 99%

“…The required aldehyde 26 was prepared through modification of a reported procedure. 42 It involves a Wittig reaction to give 25 followed by hydrogenation and aldehyde deprotection. Gratifyingly, aldehyde 26 smoothly underwent the one-pot alkynation procedure with phosphonate 24 to give a 79% yield of 27.…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

Triazole Ligands Reveal Distinct Molecular Features That Induce Histamine H₄ Receptor Affinity and Subtly Govern H₄/H₃ Subtype Selectivity

et al. 2011

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Methanesulfonyl Chloride

Vaillancourt¹,

Cudahy²,

Kreilein³

et al. 2007

Encyclopedia of Reagents for Organic Synthesis

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One‐Carbon Homologation and Homologation–Functionalization Reactions of Aldehydes

Snowden

2023

Homologation Reactions

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ω-(Imidazol-4-yl)alkane-1-sulfonamides: a new series of potent histamine H3 receptor antagonists

Cited by 11 publications

References 24 publications

Triazole Ligands Reveal Distinct Molecular Features That Induce Histamine H₄ Receptor Affinity and Subtly Govern H₄/H₃ Subtype Selectivity

Triazole Ligands Reveal Distinct Molecular Features That Induce Histamine H₄ Receptor Affinity and Subtly Govern H₄/H₃ Subtype Selectivity

Methanesulfonyl Chloride

One‐Carbon Homologation and Homologation–Functionalization Reactions of Aldehydes

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ω-(Imidazol-4-yl)alkane-1-sulfonamides: a new series of potent histamine H3 receptor antagonists

Cited by 11 publications

References 24 publications

Triazole Ligands Reveal Distinct Molecular Features That Induce Histamine H4 Receptor Affinity and Subtly Govern H4/H3 Subtype Selectivity

Triazole Ligands Reveal Distinct Molecular Features That Induce Histamine H4 Receptor Affinity and Subtly Govern H4/H3 Subtype Selectivity

Methanesulfonyl Chloride

One‐Carbon Homologation and Homologation–Functionalization Reactions of Aldehydes

Contact Info

Product

Resources

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Triazole Ligands Reveal Distinct Molecular Features That Induce Histamine H₄ Receptor Affinity and Subtly Govern H₄/H₃ Subtype Selectivity

Triazole Ligands Reveal Distinct Molecular Features That Induce Histamine H₄ Receptor Affinity and Subtly Govern H₄/H₃ Subtype Selectivity