Dépôt numérique

NMR strategies to support medicinal chemistry workflows for primary structure determination

Oguadinma, Paul, Bilodeau, François et Laplante, Steven (2017). NMR strategies to support medicinal chemistry workflows for primary structure determination Bioorganic and Medicinal Chemistry Letters , vol. 27 , nº 2. p. 242-247. DOI: 10.1016/j.bmcl.2016.11.066.

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Central to drug discovery is the correct characterization of the primary structures of compounds. In general, medicinal chemists make great synthetic and characterization efforts to deliver the intended compounds. However, there are occasions which incorrect compounds are presented, such as those reported for Bosutinib and TIC10. This may be due to a variety of reasons such as uncontrolled reaction schemes, reliance on limited characterization techniques (LC–MS and/or 1D 1H NMR spectra), or even the lack of availability or knowledge of characterization strategies. Here, we present practical NMR approaches that support medicinal chemist workflows for addressing compound characterization issues and allow for reliable primary structure determinations. These strategies serve to differentiate between regioisomers and geometric isomers, distinguish between N- versus O-alkyl analogues, and identify rotamers and atropisomers. Overall, awareness and application of these available NMR methods (e.g. HMBC/HSQC, ROESY and VT experiments, to name only a few) should help practicing chemists to reveal chemical phenomena and avoid mis-assignment of the primary structures of compounds.

Type de document: Article
Mots-clés libres: Medicinal chemistry; NMR methods; Primary structure; Regioisomers; Rotamers
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 21 févr. 2019 21:34
Dernière modification: 07 déc. 2020 14:05
URI: https://espace.inrs.ca/id/eprint/5417

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