6b4n | pdb_00006b4n

a hydroxymethyl functionality at the 4-position of the 2-phenyloxazole moiety of HIV-1 protease inhibitors involving the P2' ligands

spinqualitylabelsall models 6b4n, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6b4n is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, G53, NA Related: 2ien Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic HIV-1 protease inhibitors with rationally designed P2' ligands are described. The inhibitors are designed to enhance backbone binding interactions, particularly at the S2'-subsite. Synthesis of inhibitors was carried out efficiently. The stereochemistry of alcohol functionalities of the P2'-ligands was set by asymmetric reduction of the corresponding ketone using (R,R)- or (S,S)-Noyori's catalysts. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 3g and 3h showed an enzyme Ki of 27.9 and 49.7 pM and antiviral activity of 6.2 and 3.9 nM, respectively. These inhibitors also remained quite potent against darunavir-resistant HIV-1 variants. An X-ray structure of inhibitor 3g in complex with HIV-1 protease revealed key interactions in the S2'-subsite. Design, synthesis, biological evaluation, and X-ray studies of HIV-1 protease inhibitors with modified P2'-ligands of Darunavir.,Ghosh AK, Fyvie WS, Brindisi M, Steffey M, Agniswamy J, Wang YF, Aoki M, Amano M, Weber IT, Mitsuya H ChemMedChem. 2017 Nov 6. doi: 10.1002/cmdc.201700614. PMID:29110408 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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