Unknown

Dataset Information

0

Design, Synthesis, and X-ray Studies of Potent HIV-1 Protease Inhibitors with P2-Carboxamide Functionalities.


ABSTRACT: 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.

SUBMITTER: Ghosh AK 

PROVIDER: S-EPMC7549267 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6237192 | biostudies-literature
| S-EPMC3433276 | biostudies-literature
| S-EPMC3800042 | biostudies-literature
| S-EPMC7425579 | biostudies-literature
| S-EPMC2797486 | biostudies-literature
| S-EPMC9081228 | biostudies-literature
| S-EPMC6541917 | biostudies-literature
| S-EPMC4133278 | biostudies-literature
| S-EPMC5896574 | biostudies-literature
| S-EPMC5647257 | biostudies-literature