Synthesis of [³H]zolpidem

Abstract

Zolpidem is a novel hypnotic agent possessing a substituted imidazo [l, 2-g] pyridine structure. The synthesis of the tritium labelled compound with a specific activity of 6 0 . 5 Ci/mol is described. This new radioligand w a s initially used to establish and characterize the binding properties of Zolpidem in the rat brain.

GABAergic radioligands labelled with tritium

“…However, there have been examples of compounds that bind to the benzodiazepine site which are not structurally related to diazepam and one of these is the widely used hypnotic zolpidem ( 10 ). Zolpidem was first tritiated at nearly theoretical specific activity by Allen and co‐workers of then Synthelabo (L. E. R. S.), applying a bromination — catalytic tritium dehalogenation strategy33 affording radioligand 11 (Scheme ) which has been useful to elucidate the pharmacology of the benzodiazepine site 34–38. Perhaps the most fascinating of the GABA A positive allosteric modulators are anesthetic agents and, in particular, the potent drug ( R )‐etomidate ( 12 ).…”

One‐Pot Sequential Bromination and Fluorination to Access 3‐Fluoroimidazo[1,2‐a]pyridines from Arylketones

“…A number of pharmaceutical drugs and agrochemicals contain the imidazo[1,2‐ a ]pyridine (IMPY) scaffold These include the hypnotic drug Zolpidem, and the anti‐HIV drug GSK812397 . The radioligand 125 I‐IMPY has been used with single‐photon‐emission computed tomography (SPECT), and the fluorine‐labelled IMPY analogues FPM‐IMPY and FEM‐IMPY (Figure ) have been used with positron‐emission tomography (PET) to trace the Aβ amyloid of Alzheimer's disease …”

Synthesis and characterization of the potent cannabinoid agonist [naphthyl‐3H] WIN 55212‐2 at high specific activity

“…In preparing the compound [phenyl-3 H] zolpidem, Allen and co-workers using a similar strategy reported a specific activity of 60.5 Ci/mmol for the radioligand. 6 A proton decoupled tritium NMR (CDCl 3 ) of product 4 displayed two peaks (Figure 1), establishing the specific tritium labelling at the aromatic positions. A receptor binding assay for product 4 was reported 7 and since that time it has proven extremely useful to clarify issues regarding the cannabinoid receptor family.…”