During random screening of a small in-house library of compounds, certain substituted imidazo[1,2-a]pyridines were found to be weak allosteric inhibitors of HIV-1 reverse transcriptase (RT). A library of these compounds was prepared using the Groebke reaction and a subset of compounds prepared from 2-chlorobenzaldehyde, cyclohexyl isocyanide and a 6-substituted 2-aminopyridine showed good inhibitory activity in enzymatic (RT) and HIV anti-infectivity MAGI whole cell assays. The compound showing the best anti-HIV-1 IIIB whole cell activity (MAGI IC50 = 0.18 µM, IC90 = 1.06 µM), along with a good selectivity index (>800), was 2-(2-chlorophenyl)-3-(cyclohexylamino)imidazo[1,2-a]pyridine-5-carbonitrile 38.
Reference:
Bode, ML, Gravestock, D, Moleele, SS et al. 2011. Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors. Bioorganic and Medicinal Chemistry, Vol 19(4), pp 4227-4237
Bode, M., Gravestock, D., Moleele, S., Van der Westhuyzen, C. W., Pelly, S., Steenkamp, P., ... Nkabinde, L. (2011). Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors. http://hdl.handle.net/10204/5233
Bode, ML, D Gravestock, SS Moleele, Christiaan W Van der Westhuyzen, SC Pelly, PA Steenkamp, HC Hoppe, T Khan, and LA Nkabinde "Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors." (2011) http://hdl.handle.net/10204/5233
Bode M, Gravestock D, Moleele S, Van der Westhuyzen CW, Pelly S, Steenkamp P, et al. Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors. 2011; http://hdl.handle.net/10204/5233.
Copyright: 2011 Elsevier. This is the pre print version of the paper. The definitive version is published in Bioorganic and Medicinal Chemistry, Vol 19(4), pp 4227-4237
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