Publications by authors named "T J Perun"

The objective of the described research effort was to identify a novel serotonin and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine transporter activity and acceptable metabolic stability and exhibiting minimal drug-drug interaction. We describe herein the discovery of a series of 3-substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective SNRI in vitro and in vivo, has favorable ADME properties, and retains inhibitory activity in the formalin model of pain behavior.

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In this study, the retention behaviors of pharmaceutical and drug-like compounds in supercritical fluid chromatography (SFC) with polar stationary phases were evaluated using linear solvation energy relationships (LSERs). We used more than 200 compounds, including mono-, di-substituted benzenes, and other marketed drugs with a wide range of solvation descriptors. The dominant contribution to positive retention was the hydrogen bond donor acidity of the solutes, particularly for pyridine and amino columns.

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In this investigation the utility of evaporative light scattering detection (ELSD) combined with HPLC-MS was demonstrated as a key component of a bioassay-guided fractionation, or "biofractionation" technique, for the evaluation of high throughput screen actives. ELSD provided on-line analyte mass information that was critical for the classification of the samples. Chemiluminescent nitrogen detection (CLND) was also evaluated for sample concentration estimation for nitrogen-containing compounds, and accurate mass LC-MS-MS analysis was employed for rapid structural confirmation and elucidation of components previously identified as active via biofractionation.

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This document has been elaborated by the IUPAC Medicinal Chemistry section and is backed by a large number of scientists, many of whom have had direct involvement and whose names appear at the end of the article. This work discusses the role that the discovery of new medicinal agents has in the development of societies as well as in the conservation of biodiversity in terms of work carried out on natural products. Also included are several recommendations for countries which are presently in search of their own scientific and technological development in medicinal agents.

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Cdc25A assay-guided fractionation of a fermentation broth derived from a Streptomyces sp. resulted in the isolation of four novel naphthoquinones 1-4. Structures of these compounds were deduced by NMR and mass spectrometry.

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