Richard P. Nugent

High specific activity tritiation of several biologically active indoles

Methods are presented to synthesize and characterize [(3)H] tryptamine (1b) and [(3)H] etodolac (2c).

Tritium labelling and characterization of the cognition enhancing drug tacrine using several precursors

Tacrine and its analogues have shown promise as cognition enhancers and potential chemotherapeutic agents for Alzheimers disease. [3H]tacrine was required to explore its mechanism of action via receptor binding assay and the radioligand was prepared by means of catalytic dehalogenation of several brominated precursors.

Synthesis of some 6-keto morphinan mu opiate receptor agonists labelled with tritium at high specific activity

The high specific activity tritiation of oxymorphone and pentamorphone is described.

Potent antiviral agent WIN 54954: high specific activity labelling with tritium

Abstract Valuable antiviral compound WIN 54954 (2) was tritiated at high specific activity and the product was characterized.

Mirfentanil and A-4334: Tritiation at high specific activity

Methods are presented to synthesize and characterize [(3)H] mirfentanil and [(3)H] A-4334.

Synthesis and characterization of [N‐methyl‐3H]loperamide

Loperamide is a piperidine butyramide mu-opiate receptor agonist and currently employed to treat diarrhea. Because a single past report of tritiating loperamide was limited to only a very low specific activity product without technical details or extensive analysis, the synthesis of [N-methyl-(3)H]loperamide at high specific activity is now described in detail. An imine precursor was alkylated with [(3)H]methyl iodide to obtain a quaternary intermediate, which was then reacted with 4-(4-chlorophenyl)-4-hydroxypiperidine to afford the desired product [N-methyl-(3)H]loperamide, characterized by thin layer chromatography (TLC), HPLC, MS, UV, and proton-decoupled tritium NMR.

Generation and use of tritiated borane in situ for formamide tritiation to an N-methyl-3H group

The synthesis of [N-methyl-3 H](+/-)-mecamylamine is described as an example of a convenient and mild method to reduce formamide groups using tritiated borane generated in situ. The product was characterized by thin layer chromatography, high performance liquid chromatography, mass spectrometry, and tritium NMR.

CNS active ergot alkaloid dihydro derivatives: tritium labelling and characterization

The ergot alkaloids are an important class of medicinally useful substances and this report describes the high specific activity tritium labelling of two dihydro derivatives; namely, dihydroergotamine and dihydrobromocriptine. The former was prepared by the direct tritiation of ergotamine itself. However, efforts to perform an analogous direct tritiation on bromocriptine were unsuccessful and a multistep synthesis was required.