The enzyme reverse transcriptase (RT) is a validated target for the development of anti-HIV drugs. Drugs acting against RT may act at either the catalytic site (NRTIs) or the allosteric site (NNRTIs). During random screening of a small in-house library of compounds, a sub-set of substituted imidazo[1,2-a]pyridines were found to be allosteric inhibitors of RT. A much larger library of these compounds was prepared in order to find compounds with improved RT activity. These compounds were prepared by the Groebke reaction, an example of which is shown in Scheme 1. The preparation of the compound library will be discussed, together with the results obtained from an enzymatic RT assay as well as a cell-based anti-HIV MAGI assay. Structural elements required for RT inhibition and in silico rationalisation of these results will also be addressed.
Reference:
Bode, ML,Gravestock, D,Moleele, S, et al. 2010. Imidazo[1,2-a]pyridines as NNRTIs. 11th Frank Warren Conference of the South African Chemical Institute. Pietermaritzburg, South Africa, 17-21 January 2010, pp
Bode, M., Gravestock, D., Moleele, S., Van der Westhuyzen, C. W., Hoppe, H., Khan, T., & Pelly, S. (2010). Imidazo[1,2-a]pyridines as NNRTIs. http://hdl.handle.net/10204/4441
Bode, ML, D Gravestock, S Moleele, Christiaan W Van der Westhuyzen, H Hoppe, T Khan, and SC Pelly. "Imidazo[1,2-a]pyridines as NNRTIs." (2010): http://hdl.handle.net/10204/4441
Bode M, Gravestock D, Moleele S, Van der Westhuyzen CW, Hoppe H, Khan T, et al, Imidazo[1,2-a]pyridines as NNRTIs; 2010. http://hdl.handle.net/10204/4441 .
