Synthesis and anti-HIV activity of a bile acid analog of cosalane

Cosalane is a novel anti-HIV agent that inhibits the attachment of gp120 to CD4. The therapeutic potential of cosalane is limited by poor oral absorption. In an attempt to target the ileal bile acid transporter and thus facilitate oral bioavailability, a cosalane analog was synthesized in which the disalicylmethane pharmacophore is attached to a bile acid through a linker chain appended to C-17 of the steroid nucleus. The resulting bile acid analog of cosalane retained antiviral activity vs. HIV-1IIIB and HIV-2ROD in MT-4 cells, but was less potent than cosalane.