Summary information and primary citation
- PDB-id
- 5uj2; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- immune system-RNA
- Method
- X-ray (2.9 Å)
- Summary
- Crystal structure of hcv ns5b genotype 2a jfh-1 isolate with s15g e86q e87q c223h v321i mutations and delta8 neta hairpoin loop deletion in complex with gs-639476 (diphsohate version of gs-9813), mn2+ and symmetrical primer template 5'-auaaauuu
- Reference
- Kirschberg TA, Metobo S, Clarke MO, Aktoudianakis V, Babusis D, Barauskas O, Birkus G, Butler T, Byun D, Chin G, Doerffler E, Edwards TE, Fenaux M, Lee R, Lew W, Mish MR, Murakami E, Park Y, Squires NH, Tirunagari N, Wang T, Whitcomb M, Xu J, Yang H, Ye H, Zhang L, Appleby TC, Feng JY, Ray AS, Cho A, Kim CU (2017): "Discovery of a 2'-fluoro-2'-C-methyl C-nucleotide HCV polymerase inhibitor and a phosphoramidate prodrug with favorable properties." Bioorg. Med. Chem. Lett., 27, 1840-1847. doi: 10.1016/j.bmcl.2017.02.037.
- Abstract
- A series of 2'-fluorinated C-nucleosides were prepared and tested for anti-HCV activity. Among them, the triphosphate of 2'-fluoro-2'-C-methyl adenosine C-nucleoside (15) was a potent and selective inhibitor of the NS5B polymerase and maintained activity against the S282T resistance mutant. A number of phosphoramidate prodrugs were then prepared and evaluated leading to the identification of the 1-aminocyclobutane-1-carboxylic acid isopropyl ester variant (53) with favorable pharmacokinetic properties including efficient liver delivery in animals.
