Drug design

Lead optimisation

schema1Lead optimization is an operationally diverse stage of the drug discovery process in which the chemical structures of compounds are modified to improve besides target specificity and selectivity, also pharmacodynamic, pharmacocinetic and toxicological properties to produce a preclinical drug candidate. In this context and in order to provide new and original compounds, Greenpharma has developed innovative synthesis routes with partners.

For example, synthesis and functionalization strategies of the imidazo[1,2-b]pyrazole core were developed giving a rapid access to novel imidazo[1,2-b]pyrazole type derivatives.1,2 Some of the synthetized products were evaluated for in vitro anticancer activity using the MTT colorimetric assay against 5 human and 1 murine cancer cell lines. Promising in vitro growth inhibitory activities were exhibited by some of the target compounds.3

A new route to 6(5)-bromo- 5(6)-methylimidazo[1,2-a]imidazolin-2- ones have also been developed. Then, a novel and effective strategy of functionnalization of these scaffolds through Suzuki-Miyaura cross coupling reactions was performed.4 Thanks to this methodology, a large panel of boronic acids were easily introduced, giving access to a diversified library of 6(5)-substituted- 5(6)-methylimidazo[1,2-a] imidazolin-2- ones.


1 S. Grosse, C. Pillard, S. Massip, J.M. Léger, C. Jarry, S. Bourg, P. Bernard, G. Guillaumet, Chem. Eur. J. 2012, 18 (47), 14943-14947.
2 S. Grosse, C. Pillard, P. Bernard, G. Guillaumet Synlett 2013, 24, 2095-2101.
3 S. Grosse, V. Mathieu, C. Pillard, S. Massip, M. Marchivie, C. Jarry, P. Bernard, R. Kiss, G. Guillaumet Eur. J. Med. Chem. 2014, 84, 718-730.
4 S. Grosse, C. Pillard, F. Himbert, S. Massip, J. M. Léger, C. Jarry, P. Bernard, G. Guillaumet Eur. J. Org. Chem. 2013, 19, 4146-4155.