Abstract
Design, synthesis, biological and X-ray crystallographic studies of a series of potent HIV-1 protease inhibitors are described. Various polar functionalities have been incorporated on the tetrahydropyranyl-tetrahydrofuran-derived P2 ligand to interact with the backbone atoms in the S2-subsite. The majority of the inhibitors showed very potent enzyme inhibitory and antiviral activity. Two high-resolution X-ray structures of 30b- and 30j-bound HIV-1 protease provide insight into ligand-binding site interactions. In particular, the polar functionalities on the P2-ligand appear to form unique hydrogen bonds with Gly48 amide NH and amide carbonyl groups in the flap region.
Original language | English (US) |
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Pages (from-to) | 11607-11621 |
Number of pages | 15 |
Journal | Organic and Biomolecular Chemistry |
Volume | 13 |
Issue number | 48 |
DOIs | |
State | Published - Oct 14 2015 |
Bibliographical note
Publisher Copyright:© The Royal Society of Chemistry.