Search

Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.

In this Communication, a La Trobe University affiliation is missing for the author David A. Winkler. The penultimate author address entry must read: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052 (Australia) and La Trobe Institute for Molecular Science, La Trobe University, Bundoora, 3084 (Australia).

The methoxyamine group represents an ideal protecting group for the nitroxide moiety. It can be easily and selectively introduced in high yield (typically >90%) to a range of functionalised nitroxides using FeSO4·7H2O and H2O2 in DMSO. Its removal is readily achieved under mild conditions in high yield (70–90%) using mCPBA in a Cope-type elimination process.

We describe a novel and facile approach to covalently graft molecules containing stable free radicals onto carbon surfaces including graphene, carbon nanotubes, glassy carbon and carbon fibres. The new technique employs a stable aryl nitroxide radical diazonium tetrafluoroborate salt. The salt may be isolated and added to carbon surfaces in solution, suspension or electrochemically and represents a convenient, versatile and highly efficient means to adorn graphitic materials with large numbers of free radical spin systems.

Cubane can be considered the ideal internal standard for reactions observed by NMR, due to an almost complete benign reactivity and uniquely reliable 1H and 13C NMR resonances, in wide variety of deuterated solvents.

3- and 4-Pyridyliminopropadienones were prepared by flash vacuum thermolysis of Meldrum’s acid derivatives and characterized by low temperature IR spectroscopy. They react with dimethylamine to afford 1,5-, 1,6-, and 1,7-naphthyridones. The same naphthyridones are also obtained by microwave irradiation of the Meldrum’s acid derivatives. Quinolones were obtained by microwave irradiation of phenylaminomethylene-Meldrum’s acids and 1-phenylpyrrole-2,3-diones.