7to6 | pdb_00007to6

HIV-1 wild type protease with GRL-01717A, with C-4 substituted cyclohexane-fused bis-tetrahydrofuran (Chf-THF) derivatives as P2-ligand [diastereomer 2]

spinqualitylabelsall models 7to6, resolution 1.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7to6 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CL, G77, NA Related: 2ien, 6bz2, 7to5, 6vod, 6voe Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The design, synthesis, X-ray structural, and biological evaluation of a series of highly potent HIV-1 protease inhibitors are reported herein. These inhibitors incorporated novel cyclohexane-fused tricyclic bis -tetrahydrofuran as P2 ligands in combination with a variety of P1 and P2'-ligands. Compound 4d with a difluoromethylphenyl P1 ligand and a cyclopropylaminobenzothiazole P2' ligand exhibited the most potent antiviral activity. Also, it maintained highly potent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The corresponding inhibitor 5d with an enantiomeric ligand was significantly less potent in these antiviral assays. The new P2 ligands were synthesized in optically active form using enzymatic desymmetrization of meso -diols as the key step. To obtain molecular insight, high resolution X-ray structures of inhibitors 4b and 5d -bound HIV-1 protease were determined and structural analyses are highlighted here. Design, Synthesis and X-ray Structural Studies of Potent HIV-1 Protease Inhibitors Containing C-4 Substituted Tricyclic Hexahydro-furofuran derivatives as P2 ligands.,Ghosh AK, Kovela S, Sharma A, Shahabi D, Ghosh AK, Hopkins DR, Yadav M, Johnson ME, Agniswamy J, Wang YF, Aoki M, Amano M, Weber IT, Mitsuya H ChemMedChem. 2022 Feb 15. doi: 10.1002/cmdc.202200058. PMID:35170223 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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