Clinical validation of virus maturation inhibition as an approach to the control of HIV-1 infection was first achieved by bevirimat (BVM), a first generation maturation Inhibitor (MI). Poor polymorphic coverage as well as challenges with drug formulation prevented BVM from being further developed. BMS-955176 is a second generation HIV-1 maturation inhibitor that combines a broader spectrum of antiviral activity with good oral exposure in preclinical species. Both BVM and BMS-955176 are derivatives of the triterpenoid belutinic acid; however, key structural differences between the two compounds provided the targeted improvement in virological and pharmacokinetic profiles displayed by BMS-955176. The structure-activity studies leading to the design, synthesis, and preclinical characterization of BMS-955176 will be discussed.

Second generation HIV-1 maturation inhibitors: The discovery of BMS-955176

254th National Meeting (2017)

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