1075209-51-6Relevant articles and documents
Design, Synthesis, and X-ray Studies of Potent HIV-1 Protease Inhibitors with P2-Carboxamide Functionalities
Ghosh, Arun K.,Grillo, Alessandro,Raghavaiah, Jakka,Kovela, Satish,Johnson, Megan E.,Kneller, Daniel W.,Wang, Yuan-Fang,Hattori, Shin-Ichiro,Higashi-Kuwata, Nobuyo,Weber, Irene T.,Mitsuya, Hiroaki
, p. 1965 - 1972 (2020)
The design, synthesis, biological evaluation, and X-ray structural studies are reported for a series of highly potent HIV-1 protease inhibitors. The inhibitors incorporated stereochemically defined amide-based bicyclic and tricyclic ether derivatives as the P2 ligands with (R)-hydroxyethylaminesulfonamide transition-state isosteres. A number of inhibitors showed excellent HIV-1 protease inhibitory and antiviral activity; however, ligand combination is critical for potency. Inhibitor 4h with a difluorophenylmethyl as the P1 ligand, crown-THF-derived acetamide as the P2 ligand, and a cyclopropylaminobenzothiazole P2′-ligand displayed very potent antiviral activity and maintained excellent antiviral activity against selected multidrug-resistant HIV-1 variants. A high resolution X-ray structure of inhibitor 4h-bound HIV-1 protease provided molecular insight into the binding properties of the new inhibitor.