A level – Chirality of AWZ1066S vs AWZ1066R

Click the structures to view the 3D models

AWZ1066S is an anti-Wolbachia drug designed to treat human filariasis, a disease caused by filarial nematodes. Studies show that AWZ1066S can reduce treatment time from 4–6 weeks to just 7 days by lowering Wolbachia levels by 98%.

AWZ1066 has two enantiomers, meaning they are non-superimposable mirror images of one another and exhibit different pharmacological effects in the body. The S-enantiomer has proven to be more potent than the R-enantiomer. This difference in potency is due to the configuration of the methyl group at the 2 position of the morpholinyl side chain. In the S-enantiomer (AWZ1066S), this methyl group is positioned behind the plane of the molecule (red bond), whereas in the R-enantiomer (AWZ1066R), it is positioned in front of the plane (blue bond).

For more details of the synthesis of this drug, visit this page here.

W. D. Hong, F. Benayoud, G. L. Nixon, L. Ford, K. L. Johnston, R. H. Clare, A. Cassidy, D. A. N. Cook, A. Siu, M. Shiotani, P. J. H. Webborn, S. Kavanagh, G. Aljayyoussi, E. Murphy, A. Steven, J. Archer, D. Struever, S. J. Frohberger, A. Ehrens, M. P. Hübner, A. Hoerauf, A. P. Roberts, A. T. M. Hubbard, E. W. Tate, R. A. Serwa, S. C. Leung, L. Qie, N. G. Berry, F. Gusovsky, J. Hemingway, J. D. Turner, M. J. Taylor, S. A. Ward and P. M. O’Neill, Proceedings of the National Academy of Sciences, 2019, 116, 1414-1419.