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

Bode M.L.; Gravestock D.; Moleele S.S.; Van Der Westhuyzen C.W.; Pelly S.C.; Steenkamp P.A.; Hoppe H.C.; Khan T.; Nkabinde L.A.

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

Date

2011

Authors

Bode M.L.

Gravestock D.

Moleele S.S.

Van Der Westhuyzen C.W.

Pelly S.C.

Steenkamp P.A.

Hoppe H.C.

Khan T.

Nkabinde L.A.

Abstract

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. © 2011 Elsevier Ltd. All rights reserved.

Keywords

Antiretroviral, Groebke reaction, HIV, Imidazo[1,2-a]pyridine, NNRTI, Reverse transcriptase, 2 (2 bromophenyl) n cyclohexylimidazo[1,2 a]pyridin 3 amine, 2 (2 chlorophenyl) 3 (cyclohexylamino)imidazo[1,2 a]pyridine 5 carbonitrile, 2 (2 chlorophenyl) n cyclohexylimidazo[1,2 a]pyridin 3 amine, 2 (3 bromophenyl) n cyclohexylimidazo[1,2 a]pyridin 3 amine, 2 (3 chlorophenyl) n cyclohexylimidazo[1,2 a]pyridin 3 amine, 2 (4 bromophenyl) n cyclohexylimidazo[1,2 a]pyridin 3 amine, 2 (4 chlorophenyl) n cyclohexylimidazo[1,2 a]pyridin 3 amine, 2 aminopyridine derivative, 2 chlorobenzaldehyde, 2 sec butyl n cyclohexylimidazo[1,2 a]pyridin 3 amine, cyclohexyl isocyanide, etravirine, imidazo[1,2 a]pyridine amine derivative, isopropyl n (pentan 2 yl)imidazo[1,2 a]pyridin 3 amine, isopropyl n pentylimidazo[1,2 a]pyridin 3 amine, n butyl 2 isopropylimidazo[1,2 a]pyridin 3 amine, n cyclohexyl 2 (2 fluorophenyl)imidazo[1,2 a]pyridin 3 amine, n cyclohexyl 2 (4 fluorophenyl)imidazo[1,2 a]pyridin 3 amine, n cyclohexyl 2 [2 (trifluorophenyl)phenyl]imidazo[1,2 a]pyridin 3 amine, n cyclohexyl 2 [4 (trifluorophenyl)phenyl]imidazo[1,2 a]pyridin 3 amine, n cyclohexyl 2 cyclopropylimidazo[1,2 a]pyridin 3 amine, n cyclohexyl 2 isopropylimidazo[1,2 a]pyridin 3 amine, n cyclohexyl 2 octylimidazo[1,2 a]pyridin 3 amine, n cyclohexyl 2 phenylimidazo[1,2 a]pyridin 3 amine, n cyclopentyl 2 isopropylimidazo[1,2 a]pyridin 3 amine, nonnucleoside reverse transcriptase inhibitor, reagent, rilpivirine, RNA directed DNA polymerase, unclassified drug, unindexed drug, antiviral activity, article, controlled study, drug selectivity, drug structure, drug synthesis, drug targeting, enzyme inhibition, IC 50, molecular model, solvent effect, Human immunodeficiency virus 1

Citation

Bioorganic and Medicinal Chemistry
19
14
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