Despite the effectiveness of combination antiretroviral therapy, there is an expanding population of HIV infected patients on existing therapies whose medical needs are not completely satisfied.  Members of a previously disclosed class of oral, small molecule HIV-1 attachment inhibitors (AIs) have been shown to bind to the HIV-1 viral envelope gp120 protein and interfere with attachment to cellular CD4 receptors, the initial point of entry for the virus.  Clinical studies with BMS-488043 previously validated the AIs as a novel class of small molecules with potent activity in HIV-1-infected subjects.  This presentation will describe the further chemical optimization of BMS-488043 to realize compounds with an improved pre-clinical virology profile.  One such compound, BMS-626529, and its water soluble phosponoxymethyl prodrug, BMS-663068, were advanced into early clinical studies.  The promising clinical efficacy of the prodrug, which was enhanced by further refinements made in development, will also be discussed.

Discovery of BMS-663068, an HIV attachment inhibitor for the treatment of HIV-1

241st National Meeting (2011)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.