Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors

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 IC 50 = 0.18 μM, IC 90 = 1.06 μM), along with a good selectivity index (>800), was 2-(2-chlorophenyl)-3- (cyclohexylamino)imidazo[1,2-a]pyridine-5-carbonitrile 38. © 2011 Elsevier Ltd. All rights reserved.