Plenary Lecture 5

Title: Exploring opportunities in the chemical space to develop a library of heterocycles

Professor Flavio da Silva Emery

University of São Paulo, Brazil


Lecture Summary: There are plenty of opportunities for drug discovery and chemical biology in heterocyclic chemical space. Developing innovative heterocycles is a useful strategy for building a multipurpose library of compounds. However, synthesizing and functionalizing new heterocycles is a challenging process, and, in order to fit appropriate druglikeness and structure requirements for the designed projects, it is important to develop direct synthetic methodologies to achieve target products, in few steps and high yields. Furo[3,2-b]pyridine,2,6-naphthyridine and pyrazolo[3,4-c]pyridine are examples of under-represented fragments, that can contribute to increasing druglike chemical space for fragment-based drug discovery1,2. Synthetic strategies for obtaining these heterocycles will be presented in this lecture, alongside with modern CH-activation methodologies for fragment growth and library diversification. Fragment-based drug discovery strategies will be shown, attempting to highlight the usefulness of the developed library. On the other hand, besides druglike properties, heterocycles can be used as chemical probes for biology studies due to electronic and fluorescence properties. Borodipyrromethenes (BODIPY®) are interesting examples of fluorescent heterocycles due to chemical stability, fluorescence versatility and reactivity3, which can be explored for the rational design of innovative fluorophores. The lecture will show the development of a library of BODIPYs® and further applications in chemical biology, drug delivery, and pharmacology4. In summary, structural and functional diversity of heterocycles will be shown, trying to explore the chemical space to find opportunities for innovation.


Acknowledgments: F. S. Emery would like to acknowledge FAPESP, CNPq, CAPES and Astex Therapeutics for the financial support.


References: [1]Silva Junior, P. E., Rezende, L. C. D., Gimenes, J. P., Maltarollo, V. G., Dale, J., Trossini, G. H. G., Emery, F. S.  and Ganesan, A. RSC Advances2016, 6, 22777-22780.

2Fumagalli, F.; Emery, F. S.J. Org. Chem. 2016, Article ASAP 10.1021/acs.joc.6b01329.

3. Rezende, L. C. D., Emery, F. S. Orbital Elec. J. Chem.2013, 5 (1), 62-83.

4. Rezende, L. C. D., Melo, S. G., Boodts, S., Verbelen, B., Dehaen, W. Emery, F. S.Org. Biomol. Chem.2015, 13 (21), 6031-6038.