Design, synthesis, and evaluation of indole compounds as novel inhibitors targeting Gp41

A series of indole ring containing compounds were designed based on the structure of the gp41 complex in the region of the hydrophobic pocket. These compounds were synthesized using a Suzuki Coupling reaction, and evaluated using a fluorescence binding assay and cell–cell fusion assay. The observed inhibition constant of compound 7 was 2.1 μM, and the IC50 for cell–cell fusion inhibition was 1.1 μM. Assay data indicated that 7 is a promising lead compound for optimization into an effective low molecular weight fusion inhibitor.

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