1450609-07-0Relevant academic research and scientific papers
Highly potent HIV-1 protease inhibitors with novel tricyclic P2 ligands: Design, synthesis, and protein-ligand X-ray studies
Ghosh, Arun K.,Parham, Garth L.,Martyr, Cuthbert D.,Nyalapatla, Prasanth R.,Osswald, Heather L.,Agniswamy, Johnson,Wang, Yuan-Fang,Amano, Masayuki,Weber, Irene T.,Mitsuya, Hiroaki
, p. 6792 - 6802 (2013/10/01)
The design, synthesis, and biological evaluation of a series of HIV-1 protease inhibitors incorporating stereochemically defined fused tricyclic P2 ligands are described. Various substituent effects were investigated to maximize the ligand-binding site interactions in the protease active site. Inhibitors 16a and 16f showed excellent enzyme inhibitory and antiviral activity, although the incorporation of sulfone functionality resulted in a decrease in potency. Both inhibitors 16a and 16f maintained activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 16a-bound HIV-1 protease revealed important molecular insights into the ligand-binding site interactions, which may account for the inhibitor's potent antiviral activity and excellent resistance profiles.
