Towards the Synthesis of 1,3-Azaborines as Potential HIV-1 Protease Inhibitors

Drug discovery for HIV/AIDS has resulted in many life-saving therapies, making a great impact on modern medicine. Even though new therapies are constantly being developed, many drugs are highly susceptible to resistance development, have poor bioavailability, and cause several side effects. With that in mind, there is an urgent need for the development of new types of inhibitory compounds that have better resistance profiles, higher bioavailability, higher affinity and lower toxicity. The use of boron in medicinal chemistry has been growing substantially over the last decade since the development of the first FDA approved drug, Velcade, in 2003. Boron containing compounds have been previously overlooked due to preconceived notions regarding boron’s toxicity. With those ideas resolved, boron is being implemented in modern pharmaceutical therapeutics for a variety of diseases. Regarding HIV/AIDS, novel cyclic boronates are currently being synthesized with the intention of acting as dual-mode, both competitive and associative, inhibitors of the HIV-1 protease. The boronated analogues are being synthesized with the intent that they will demonstrate greater inhibitory activity than their non-boronated analogs. For this presentation, Nicholas Treich received a College of the Sciences Best Oral Presentation Award for 2014