High-dilution cyclization of polyoxapentacosanodinitriles

Newman, Melvin S.; Barbee, T. G.; Blakesley, C. Newton; Ziauddin, .; Gromelski, Stanley; Khanna, Vinod Kumar; Lee, Len-Fang; Radhakrishnan, J.; Robey, Roger L.

doi:10.1021/jo00908a003

Cited by 12 publications

(2 citation statements)

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“…The synthesis of the linker (Scheme B), which is necessary for the connection of the pharmacophore with the fluorophore, started from the commercially available tetraethylene glycol 6 . In the first step, mesylate groups were introduced ( 7 ) as good leaving groups, followed by subsequent treatment with sodium azide to afford 8 . , A selective “Staudinger”-type reduction of a single azide group in a biphasic water/ethyl acetate mixture afforded the final linker 9 with 77% yield …”

Section: Resultsmentioning

confidence: 99%

“…In the first step, mesylate groups were introduced (7) as good leaving groups, followed by subsequent treatment with sodium azide to afford 8. 32,33 A selective "Staudinger"-type reduction of a single azide group in a biphasic water/ethyl acetate mixture afforded the final linker 9 with 77% yield. 34 Subsequently, 5 was coupled with 9 using EDC/HOBt as coupling reagents under microwave irradiation to afford product 10, 26 which was reduced to the primary amine 11 by a "Staudinger" reaction (Scheme 2).…”

Section: ■ Introductionmentioning

confidence: 99%

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A Versatile Sub-Nanomolar Fluorescent Ligand Enables NanoBRET Binding Studies and Single-Molecule Microscopy at the Histamine H₃ Receptor

et al. 2021

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The histamine H 3 receptor (H 3 R) is considered an attractive drug target for various neurological diseases. We here report the synthesis of UR-NR266, a novel fluorescent H 3 R ligand. Broad pharmacological characterization revealed UR-NR266 as a sub-nanomolar compound at the H 3 R with an exceptional selectivity profile within the histamine receptor family. The presented neutral antagonist showed fast association to its target and complete dissociation in kinetic binding studies. Detailed characterization of standard H 3 R ligands in NanoBRET competition binding using UR-NR266 highlights its value as a versatile pharmacological tool to analyze future H 3 R ligands. The low nonspecific binding observed in all experiments could also be verified in TIRF and confocal microscopy. This fluorescent probe allows the highly specific analysis of native H 3 R in various assays ranging from optical high throughput technologies to biophysical analyses and single-molecule studies in its natural environment. An off-target screening at 14 receptors revealed UR-NR266 as a selective compound.

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Section: Resultsmentioning

confidence: 99%