David Gravestock

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.

Expeditious synthesis and biological evaluation of novel 2,N6-disubstituted 1,2-dihydro-1,3,5-triazine-4,6-diamines as potential antimalarials.

A small set of novel 2,N6-disubstituted 1,2-dihydro-1,3,5-triazine-4,6-diamines was prepared possessing a flexible tether between the exocyclic nitrogen bonded to C-6 of the 1,2-dihydro-1,3,5-triazine-4,6-diamine heterocycle and the distal aryl ring. Three zones were varied in this series of compounds, namely the nature of the substituent(s) on C-2; the nature of the substituent(s) on the distal aryl ring; as well as the nature and length of the flexible tether between the rings. The compound showing the best antimalarial activity (cycloguanil-resistant FCR-3 Plasmodium falciparum IC50=0.99 μM) was N6-(3-(4-chlorophenoxy)propyl)-2-(furan-2-yl)-1,2-dihydro-1,3,5-triazine-4,6-diamine hydrochloride.

Synthesis, Reactions and Uses of Isocyanides in Organic Synthesis. An Update

Isocyanides were formally discovered by Gautier1 and Hofmann2 in 1867 but the history of isocyanide chemistry in fact predates this discovery. Lieke carried out the first isocyanide synthesis in 18...