| Structural highlights
3cde is a 2 chain structure with sequence from Hepatitis c virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: |
| | Related: | 3bsc, 3br9, 3bsa |
| Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. Lead optimization led to the discovery of compound 3a, which displayed potent inhibitory activities in biochemical and replicon assays [IC(50) (1b)<10nM; IC(50) (1a)=22 nM; EC(50) (1b)=5nM], good stability toward human liver microsomes (HLM t(1/2)>60 min), and high ratios of liver to plasma concentrations 12h after a single oral administration to rats.
Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)- 5-hydroxy-2H-pyridazin-3-ones. Part 3: Further optimization of the 2-, 6-, and 7'-substituents and initial pharmacokinetic assessments.,Li LS, Zhou Y, Murphy DE, Stankovic N, Zhao J, Dragovich PS, Bertolini T, Sun Z, Ayida B, Tran CV, Ruebsam F, Webber SE, Shah AM, Tsan M, Showalter RE, Patel R, Lebrun LA, Bartkowski DM, Nolan TG, Norris DA, Kamran R, Brooks J, Sergeeva MV, Kirkovsky L, Zhao Q, Kissinger CR Bioorg Med Chem Lett. 2008 Jun 1;18(11):3446-55. Epub 2008 Mar 5. PMID:18457949[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li LS, Zhou Y, Murphy DE, Stankovic N, Zhao J, Dragovich PS, Bertolini T, Sun Z, Ayida B, Tran CV, Ruebsam F, Webber SE, Shah AM, Tsan M, Showalter RE, Patel R, Lebrun LA, Bartkowski DM, Nolan TG, Norris DA, Kamran R, Brooks J, Sergeeva MV, Kirkovsky L, Zhao Q, Kissinger CR. Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)- 5-hydroxy-2H-pyridazin-3-ones. Part 3: Further optimization of the 2-, 6-, and 7'-substituents and initial pharmacokinetic assessments. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3446-55. Epub 2008 Mar 5. PMID:18457949 doi:10.1016/j.bmcl.2008.02.072
|
