Synthesis of a cosalane analog with an extended polyanionic pharmacophore conferring enhanced potency as an anti-HIV agent

A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 μM as an inhibitor of the cytopathic effect of HIV-1 in CEM-SS cells, which represents a significant increase in potency over cosalane itself (EC50 5.1 μM). Both cosalane and the new analog are inhibitors of viral entry into target cells.