Inhibitors of HIV-1 attachment. Part 8: The effect of C7-heteroaryl substitution on the potency, and in vitro and in vivo profiles of indole-based inhibitors

Optimization of the early lead compound 2 with heteroaryl substitution at the C7 position identified inhibitors with picomolar inhibitory activity. These C7-heteroaryl-indole analogs maintained the ligand efficiency (LE) of 2 and were also lipophilic efficient as measured by LLE and LELP. The highly permeable 1,2,4-oxadiazole analog 13 exhibited the highest oral exposure in rats.