title: Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors.
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 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.
authors.affiliation: CSIR Biosciences, Private Bag X2, Modderfontein, Johannesburg 1645, South Africa. mbode@csir.co.za
authors.forename: Moira L
authors.initials: ML
authors.lastname: Bode
authors.forename: David
authors.initials: D
authors.lastname: Gravestock
authors.forename: Simon S
authors.initials: SS
authors.lastname: Moleele
authors.forename: Christiaan W
authors.initials: CW
authors.lastname: van der Westhuyzen
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pelly
authors.forename: Paul A
authors.initials: PA
authors.lastname: Steenkamp
authors.forename: Heinrich C
authors.initials: HC
authors.lastname: Hoppe
authors.forename: Tasmiyah
authors.initials: T
authors.lastname: Khan
authors.forename: Lindiwe A
authors.initials: LA
authors.lastname: Nkabinde
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C568688:2-(2-chlorophenyl)-3-(cyclohexylamino)imidazo(1,2-a)pyridine-5-carbonitrile; D007093:Imidazoles; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D054852:Small Molecule Libraries; D054303:HIV Reverse Transcriptase