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2‘,6‘-Dimethylphenoxyacetyl: A New Achiral High Affinity P 3 -P 2 Ligand for Peptidomimetic-Based HIV Protease Inhibitors
✍ Scribed by Beaulieu, Pierre L.; Anderson, Paul C.; Cameron, Dale R.; Croteau, Gilbert; Gorys, Vida; Grand-Maître, Chantal; Lamarre, Daniel; Liard, Francine; Paris, William; Plamondon, Louis; Soucy, François; Thibeault, Diane; Wernic, Dominik; Yoakim, Christiane; Pav, Susan; Tong, Liang
- Book ID
- 127040324
- Publisher
- American Chemical Society
- Year
- 2000
- Tongue
- English
- Weight
- 712 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0022-2623
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The hexahydrofurofuranyloxy group was evaluated as a conformationally constrained P2 ligand for symmetry-based HIV protease inhibitors. A number of compounds showed nM level activity against HIV in MT4 cells and lower protein binding than the licensed protease inhibitor ritonavir. However, replaceme
A combination of structure-activity studies, kinetic analysis, X-ray crystallographic analysis, and modeling were employed in the design of a novel series of HIV-1 protease (HIV PR) inhibitors. The crystal structure of a complex of HIV PR with SRSS-2,5-bis[N-(tert-butyloxycarbonyl)amino]-3,4-dihydro